Palladium-catalyzed oligocyclizations of 2-bromoalka-1,(n+m+1)-dien-(n+1)- ynes - Influence of tether lengths and substituents on the outcome of the reaction (Part II)

Article abstract of DOI:10.1002/ejoc.201000578

The cascade reaction modes and hence the outcomes of the palladium-catalyzed oligocyclizations of various 2-bromoalka- 1,(n+m+1)-diene-(n+1)-yne substrates were found to be highly dependent on the tether lengths between the multiple bond fragments, and on the nature of the substituent at the non-brominated vinylic terminus. Just like 2-bromododeca- 1,11-dien-6-ynes with their two three-atom tethers, 2-bromotrideca- 1,12-dien-7-ynes 8 and 2-bromotetradeca-1,13-dien- 8-ynes 17, with combinations of four- and three- as well as five- and three-atom tethers, under Heck-type reaction conditions undergo, after the initial oxidative addition step, two consecutive n-exo-dig and m-exo-trig carbopalladations followed by β-hydride elimination and ensuing 6π-electro- cyclization to furnish tricyclic bisannelated cyclohexadiene derivatives, such as 37 and 40, in moderate yields (30 and 29%). On the other hand, when 2-bromoalka-1,(n+m+1)- dienynes with a four-, five- or even a six-atom tether between the bromoene and the yne moiety, and a four-atom tether between the yne and the terminal ene unit, such as 34, 35 and 36, are subjected to Heck-type reaction conditions, they undergo a cascade oligocyclization involving a 5-exo-trigand ensuing 3-exo-trig-carbopalladation as the fourth and fifth steps before the terminating β-hydride elimination, eventually leading to tetracyclic skeletons such as 43, 44 and 45 with a bridging three-membered ring in yields of 74, 76 and 32%, respectively.

Full text of DOI:10.1002/ejoc.201000578

FULL PAPER
DOI: 10.1002/ejoc.201000578
Palladium-Catalyzed Oligocyclizations of 2-Bromoalka-1,(n+m+1)-dien-(n+1)-
ynes – Influence of Tether Lengths and Substituents on the Outcome of the
Reaction (Part II)
Stefan Schweizer,[a] Wajdi M. Tokan,[a][‡] Philip J. Parsons,[b] and Armin de Meijere*[a]
Dedicated to Professor Dr. Carmen Najera on the occasion of her 60th birthday
Keywords: Homogenous catalysis / Domino reactions / Palladium catalysis / Carbooligocyclization / Dienyne
The cascade reaction modes and hence the outcomes of the
palladium-catalyzed oligocyclizations of various 2-bromo-
alka-1,(n+m+1)-diene-(n+1)-yne substrates were found to be
highly dependent on the tether lengths between the multiple
bond fragments, and on the nature of the substituent at the
non-brominated vinylic terminus. Just like 2-bromododeca-
cyclization to furnish tricyclic bisannelated cyclohexadiene
derivatives, such as 37 and 40, in moderate yields (30 and
29%). On the other hand, when 2-bromoalka-1,(n+m+1)-di-
enynes with a four-, five- or even a six-atom tether between
the bromoene and the yne moiety, and a four-atom tether
between the yne and the terminal ene unit, such as 34, 35
1,11-dien-6-ynes with their two three-atom tethers, 2-bromo- and 36, are subjected to Heck-type reaction conditions, they
trideca-1,12-dien-7-ynes 8 and 2-bromotetradeca-1,13-dien-
8-ynes 17, with combinations of four- and three- as well as
five- and three-atom tethers, under Heck-type reaction con-
ditions undergo, after the initial oxidative addition step, two
consecutive n-exo-dig and m-exo-trig carbopalladations fol-
lowed by β-hydride elimination and ensuing 6π-electro-
undergo a cascade oligocyclization involving a 5-exo-trig-
and ensuing 3-exo-trig-carbopalladation as the fourth and
fifth steps before the terminating β-hydride elimination,
eventually leading to tetracyclic skeletons such as 43, 44 and
45 with a bridging three-membered ring in yields of 74, 76
and 32%, respectively.
ated cyclohexadiene derivatives of type 2 or tetracyclic skel-
etons of type 3 with a bridge-annelated cyclopropane moi-
ety between rings A and B ring (Scheme 1).
Introduction
Transition metal-catalyzed so-called cascade or domino
reactions[1] are efficient ways of constructing complex car-
bon frameworks in a single one-pot operation. In this con-
text, several transition metals[2] have been utilized to induce
different cascade modes to provide a diversity of complex,
mostly oligocyclic compounds the access to which, other-
wise, would be difficult. Yet, palladium-catalyzed cascade
oligocyclizations of open-chain substrates, containing sev-
eral multiple bond fragments, under Heck-type reaction[3]
and cycloisomerization conditions[4,5] have been among the
most extensively studied processes in this area.
As has previously been reported by our own group,[6]
different 2-bromodienyne substrates of the general type 1
can undergo mainly two modes of palladium-catalyzed cas-
cade oligocyclizations to furnish either tricyclic bisannel-
Scheme 1. Two modes of palladium-catalyzed intramolecular oligo-
cyclizations of 2-bromodienynes.
In addition, more recently we disclosed[7] that the mech-
anistic pathways and hence the outcomes of the palladium-
catalyzed cascade oligocyclizations of 2-bromoalk-1-ene-
(n+1),(m+n+1)-diynes can be determined by the tether
lengths between each two pairs of multiple bond fragments
and the nature of the substituent at the acetylene terminus.
[a] Institut für Organische und Biomolekulare Chemie der Georg-
August-Universität Göttingen,
Tammannstrasse 2, 37077 Göttingen, Germany
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
[b] Department of Chemistry, University of Sussex,
Brighton, UK
[‡] Current address: Al-Balqa’ Applied University,
As-salt, Jordan
Eur. J. Org. Chem. 2010, 4687–4699
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4687

S. Schweizer, W. M. Tokan, P. J. Parsons, A. de Meijere
FULL PAPER
The current study, accordingly, has been conducted to generated propargyl alkoxide with methyl iodide furnished
explore the effect of the tether lengths and the nature of the diethyl 2-bromo-8-methoxytrideca-1,12-dien-6-yne-4,4-di-
terminal substituents on determining the modes of palla- carboxylate (11) in 70% overall yield from 9 (Scheme 3).
dium-catalyzed cascade oligocyclizations of 2-bromoalka-
1,(n+m+1)-diene-(n+1)-ynes.[8]
Results and Discussion
Preparation of the Oligocyclization Substrates
Scheme 3. Synthesis of diethyl 2-bromo-8-methoxytrideca-1,12-
dien-6-yne-4,4-dicarboxylate with a three- and a four-atom tether
between the vinyl bromide as well as the terminal alkene moiety,
Substrates containing a three-atom and a four-atom
tether between the vinyl bromide moiety as well as the ter-
minal alkene and the internal acetylene were prepared by
deprotonating tetrahydropyranyl-protected but-3-yn-1-ol
(4) at –78 °C with n-butyllithium and treating the resulting
lithium acetylide with 5-bromo-1-pentene (5) to furnish 2-
respectively, and the internal acetylene. A: 1) nBuLi, THF, –78 °C,
10 min, 2) 5-hexenal (7), –78Ǟ0 °C, 30 min; B: MeI, DMSO, 0 °C,
2 h (E = CO2Et).
A cyclization precursor with a five- and a three-atom
tether between each pair of multiple bonds was prepared
by alkylating sodium diethyl malonate enolate with 5-bro-
mopentyne (12) to produce diethyl 2-(5-pentynyl)malonate
(13). The sodium enolate of the latter was allylated with
2,3-dibromopropene to afford the 2-bromonon-1-en-8-yne
derivative 14. The enyne 14 was then deprotonated at
–78 °C with n-butyllithium, and the resulting lithium acet-
ylide was added to the carbonyl group of 2,2-dimethyl-4-
pentenal (15)[10] to provide the propargyl alcohol 16 which,
upon Swern oxidation, furnished diethyl 2-bromo-11,11-di-
methyl-10-oxotetradeca-1,13-dien-8-yne-4,4-dicarboxylate
(17) in 72% yield (Scheme 4).
(8Ј-nonen-3Ј-ynyloxy)tetrahydro-2H-pyran. Following
a
published procedure,[9] the tetrahydropyranyloxy group was
directly converted into a bromine substituent by treating the
acetal at –20 °C in dichloromethane with triphenylphos-
phane and bromine to give 9-bromo-1-nonen-6-yne (6) in
56% yield over both steps from 4. The bromoenyne 6 was
then used to alkylate diethyl malonate enolate at ambient
temperature in dimethylformamide (DMF) to produce di-
ethyl 2-(8Ј-nonen-3Ј-ynyl)malonate (7) in 72% yield. The
sodium enolate of 7 was subsequently allylated with 2,3-
dibromopropene in dimethoxyethane (DME), which turned
out to provide a higher yield (81%) of the desired diethyl
2-bromotrideca-1,12-dien-7-yne-4,4-dicarboxylate (8) than
when working in dimethylformamide (DMF) (Scheme 2).
Scheme 2. Synthesis of diethyl 2-bromotrideca-1,12-dien-7-yne-4,4-
dicarboxylate with a four- and a three-atom tether connecting the
vinyl bromide and the terminal alkene moiety, respectively, with the
internal acetylene. A: 1) nBuLi, THF, –78 °C, 10 min 2) 5-bromo-
1-pentene (2), HMPA, –78 °CǞ room temp., 24 h; B: PPh3, Br2,
CH2Cl2, –20 °CǞ room temp., 24 h. C: NaH, dimethyl malonate,
DMF, room temp., 24 h, D: NaH, 2,3-dibromopropene, DME,
room temp., 12 h (E = CO2Me).
Scheme 4. Synthesis of diethyl 2-bromo-10-methoxytetradeca-1,13-
dien-8-yne-4,4-dicarboxylate with a five- and a three-atom tether
between the vinyl bromide as well as the terminal alkene moiety,
respectively, and the internal acetylene. A: diethyl malonate, NaH,
DMF, room temp., 2 d; B: 1) NaH, DME 2) 2,3-dibromopropene,
room temp., 2 h; C: 1) nBuLi, THF, –78 °C, 10 min, 2) 2,2-di-
methyl-4-pentenal (15), –78Ǟ20 °C, 30 min; D: (COCl)2, DMSO,
Et3N, CH2Cl2, –60Ǟ20 °C (E = CO2Et).
Another substrate with a four- and a three-atom tether
between each pair of multiple bonds, but in reverse order
than 8, was also prepared. Deprotonation of the previously
described diethyl 2-(2Ј-bromoallyl)-2-(2ЈЈ-propynyl)malon-
An additional substrate with a five- and a three-atom
ate (9)[6d] at –78 °C with n-butyllithium, subsequent ad- tether, but with an oxygen atom in the former, was prepared
dition of the resulting lithium acetylide to the carbonyl in a similar way. Following a published procedure,[11] 4-pen-
group of 5-hexenal (10) and in situ methylation of the newly tynol (18) was converted into the ether 19 with 2,3-dibro-
4688
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4687–4699

Palladium-Catalyzed Oligocyclizations
mopropene at ambient temperature in dichloromethane/ 23 by deprotonation with n-butyllithium at –78 °C, with 6-
water employing sodium hydroxide and cetyltrimethylam- bromo-1-hexene (24) in 71, 82, and 43% yield, respectively.
monium bromide (CETAB) as a phase-transfer catalyst. The tetrahydropyranyloxy groups in 25–27 were directly
The resulting 5-(2Ј-bromoallyloxy)pent-1-yne (19) was sub- converted into bromine substituents, and the resulting alk-
jected to the same sequence of reactions as for the prepara- enynyl bromides 28–30 were used to alkylate sodium diethyl
tion of 17 from the enyne 14, to furnish the targeted 10-(2Ј- malonate enolate to provide 31, 32, and 33 in 64, 59, 77%
bromoallyloxy)-5-methoxy-4,4-dimethyl-1-decen-6-yne (20) yield, respectively. The latter were allylated with 2,3-dibro-
in 93% overall yield (Scheme 5).
mopropene to furnish the desired diethyl 2-bromoalka-
1,(n+7)-dien-(n+1)-yne-4,4-dicarboxylates 34, 35, and 36 in
83, 76, and 66% yield, respectively (Scheme 6).
Palladium-Catalyzed Oligocyclizations
When substrates each with one three- and one four-atom
tether 8 and 11, respectively, were treated in acetonitrile at
80 °C with palladium acetate (5–10 mol-%), triphenylphos-
phane (10–25 mol-%), and silver carbonate (3 equiv.) for
16–34 hours, all the starting material was consumed and
the tricyclic compounds 37 and 39 with one five- and one
six-membered ring annelated to a central cyclohexadiene
moiety were isolated in 30 and 37% yield, respectively; in
addition to 37, the aromatic product 38 (18% yield), re-
sulting from dehydrogenation of 37, was formed
(Scheme 7).
Scheme 5. Synthesis of 10-(2Ј-bromoallyloxy)-5-methoxy-4,4-di-
methyl-1-decen-6-yne (20) with an oxygen-containing five-atom
tether. A: 2,3-dibromopropene, NaOH, CETAB, H2O, CH2Cl2,
20 °C, 6 h; B: 1) nBuLi, THF, –78 °C, 10 min, 2) 2,2-dimethyl-4-
pentenal (15), –78Ǟ20 °C, 30 min, 3) MeI, DMSO, 0 °C, 2 h.
The dienynes 17 and 20, each with a five- and a three-
Three cyclization precursors, all with a tetramethylene atom tether, under similar conditions also led to the con-
chain between the terminal alkene and the internal acetyl- sumption of all the starting material and gave the bisannel-
ene, but with four-, five- and six-atom tethers connecting ated cyclohexadienes 40 (33%) and 41 (43%), respectively,
the vinyl bromide moiety and the internal alkyne, were ac- along with the dehydrogenation product 42 (5%) in the lat-
cessed via the tetrahydropyranyl-protected alk-1-en-7-yn- ter case (Scheme 8). However, these transformations re-
(n+4)-ols 25–27 obtained by alkylating the lithium acet- quired rather long reaction times, namely 4 days in the case
ylides, generated from the tetrahydropyranyloxyalkynes 21– of 17 in acetonitrile and 10 days in the case of 20 in DMF.
Scheme 6. Synthesis of diethyl 2-bromoalka-1,(n+7)-dien-(n+1)-yn-4,4-dicarboxylates each with a tetramethylene linker between the ter-
minal alkene and the internal alkyne unit and a four-, five-, and six-atom tether between the vinyl bromide and the internal acetylene.
A: 1) nBuLi, THF, –78 °C, 10 min, 2) 6-bromo-1-hexene (21), HMPA, –78 °CǞ room temp., 24 h; B: PPh3, Br2, CH2Cl2, –20 °CǞ room
temp., 24 h. C: NaH, diethyl malonate, DMF, room temp., 24 h, D: NaH, 2,3-dibromopropene, DME, room temp., 4 h (E = CO2Et).
Eur. J. Org. Chem. 2010, 4687–4699
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4689

S. Schweizer, W. M. Tokan, P. J. Parsons, A. de Meijere
FULL PAPER
Scheme 9. Palladium-catalyzed oligocyclizations of diethyl 2-bro-
moalka-1,(n+7)-dien-(n+1)-yne-4,4-dicarboxylates with
a four-,
five-, and six-atom tether between the vinyl bromide moiety and
the internal acetylene as well as a tetramethylene linker between
the acetylene and the terminal alkene moiety. A: Pd(OAc)2 (10 mol-
%), PPh3 (25 mol-%), Ag2CO3 (1.5 equiv.), MeCN, 80 °C (E =
CO2Me).
Scheme 7. Palladium-catalyzed oligocyclizations of diethyl 2-bro-
motrideca-1,12-dien-n-yn-4,4-dicarboxylates (8, n = 7) and (11, n
= 6) with one three- and one four-atom tether. A: Pd(OAc)2
(10 mol-%), PPh3 (25 mol-%), Ag2CO3 (3 equiv.), MeCN, 80 °C; B:
Pd(OAc)2 (5 mol-%), PPh3 (10 mol-%), Ag2CO3 (3 equiv.), MeCN,
80 °C (E = CO2Me).
Discussion
All the palladium-catalyzed cascade oligocyclizations of
The thus formed tricyclic systems could easily be iden- 2-bromoalka-1,(n+m+1)-dien-(n+1)-ynes 50 are triggered
tified on the basis of their 13C NMR spectra compared to by an oxidative addition of the vinyl bromide moiety to an
those of the starting materials. The disappearance of the in situ produced Pd0 species. This will be followed by an n-
acetylenic carbon signals and the appearance of four new exo-dig carbopalladation of the triple bond to provide a
signals of quaternary olefinic carbon atoms provide a dienylpalladium bromide 51 with a tethered alkenyl side
strong evidence for the formation of tricyclic systems with chain. This intermediate may undergo either an intramolec-
two tetrasubstituted double bonds.
ular [4+2] cycloaddition with subsequent dehydropallad-
Acyclic 2-bromoalka-1,(n+7)-dien-(n+1)-ynes with more ation to produce the tricyclic systems 55 and 56 via the
than three atoms in both tethers between each pair of mul- tricyclic π-allylpalladium intermediate 53 (Scheme 10, route
tiple bonds, undergo palladium-catalyzed oligocyclization A). The latter can also arise from 6-endo-trig carbopallad-
by a different mode, as evidenced by the transformation of ation in the σ-alkylpalladium intermediate 52 (route B),
the substrates 34–36. Instead of bisannelated cyclohexa- which would be formed by m-exo-trig carbopalladation in
dienes, they yield tetracycles with a central five-membered 51. The intermediate 52 can also undergo β-hydride elimi-
ring and a cyclopropane moiety attached to the bridge be- nation to furnish the bicyclic 1,3,5-hexatriene 54, which
tween the first formed and this ring. Thus, when 34–36, subsequently yields the tricyclic diene 56 by 6π-electrocy-
respectively, were treated with a palladium precatalyst sys- clization (Scheme 10, route C). The ultimate possible reaction
tem typically employed for Heck reactions [Pd(OAc)2 mode for the intermediate 52 is to undergo a further 5-exo-
(10 mol-%), PPh3 (25 mol-%), Ag2CO3 (1.5 equiv.), MeCN], trig carbopalladation to yield the neopentyl-type σ-alkyl-
compounds 43, 44, and 45 were isolated in 74, 76 and 32% palladium species 49 which has no choice but to perform
yield, respectively (Scheme 9).
a 3-exo-trig carbopalladation to furnish the tetracyclic σ-
Scheme 8. Palladium-catalyzed oligocyclizations of 2-bromo-11,11-dimethyl-10-methoxytetradeca-1,13-dien-8-ynes each with one three-
and one five-atom tether. A: Pd(OAc)2 (10 mol-%),PPh3 (25 mol-%), Ag2CO3 (1.5 equiv.), MeCN, 80 °C; B: Pd(OAc)2 (10 mol-%), PPh3
(25 mol-%), Ag2CO3 (3 equiv.), DMF, 80 °C (E = CO2Me).
4690
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4687–4699

Palladium-Catalyzed Oligocyclizations
alkylpalladium complex 47 which, by β-hydride elimination, formed ring in order for it to coordinate and eventually
eventually yields the cyclopropane-bridged tetracycles 46 insert into this group. This situation turns up when the in-
and/or 48, depending on whether the bridgehead substitu- termediate of type 52 comprises two six-membered rings.
ent R3 is an alkyl group or a hydrogen atom (Scheme 10, However, a σ-alkylpalladium intermediate of type 52 with
route D).
at least one five-membered ring arising from a three-atom
tether will be nearly coplanar with respect to the exomethy-
lene group and, hence, it will not be in a suitable orientation
to coordinate and to insert into this group (Scheme 10,
route C).
Accordingly, the preferred conformation of the interme-
diates of type 52 comprising one five- and one six- (n = 5,
m = 6), (n = 6, m = 5) or even seven-membered ring (n =
7, m = 5) will be dominated by the geometry of the five-
membered ring and the plane of the square-planar σ-alkyl-
palladium complex will be nearly coplanar to the exometh-
ylene group (Figure 1). Consequently, products 37, 39, 40
and 41 from the corresponding acyclic precursors 8, 11, 17
and 20 also arise by two cyclizing carbopalladations to fur-
nish the intermediates of type 52 which preferably undergo
dehydropalladation and ensuing 6π-electrocyclization.
Figure 1. Optimized conformations of the intermediates of type 52
containing at least one five-membered ring.
On the other hand, the preferred conformation of inter-
mediates of type 52 comprising one six- and a second six-
(n = 6, m = 6), a seven- (n = 7, m = 6) or even an eight-
membered ring (n = 8, m = 6) will put the square-planar σ-
alkylpalladium fragment in a suitable position to coordi-
nate the exomethylene group (Figure 2) and insert into it in
a 5-exo-trig mode (Scheme 10, route D). Therefore, bromo-
dienynes 34, 35, and 36 all undergo cascade transformations
via 52 along route D (Scheme 10) to provide tetracyclic
products 43, 44 and 45, respectively.
Scheme 10. Possible pathways for cascade oligocyclizations of 2-
bromoalka-1,(n+m+1)-diene-(n+1)-ynes (50). n = 5, 6, 7,and 8; m
= 5 or 6.
The formation of tetracyclic products such as 46 and 48
from the appropriate precursors indicates that the third car-
bopalladation step, when it occurs, prefers the 5-exo-trig
rather than the 6-endo-trig mode. In addition, the intramo-
lecular [4+2] cycloaddition in 51 (route A, Scheme 10) ap-
parently is not a favored route, unless the non-brominated
terminal vinyl moiety bears an activating electron-with-
drawing group.[6d]
Figure 2. Optimized conformations of the intermediates of type 52
containing one six-membered ring and a second six-membered or
one six-membered and one larger ring.
Conclusions
As has been reported recently,[7] the square-planar inter-
This study complements the previously initiated system-
mediate σ-alkylpalladium complex 52 arising after the sec- atic variation of substituents and tether lengths in 2-bro-
ond carbopalladation step, must be in a non-coplanar ori- moalka-1,(n+m+1)-dien-(n+1)-ynes and their effect on the
entation with respect to the exomethylene group on the first outcome of the palladium-catalyzed cascade oligocycliza-
Eur. J. Org. Chem. 2010, 4687–4699
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4691

S. Schweizer, W. M. Tokan, P. J. Parsons, A. de Meijere
FULL PAPER
ture was diluted with water (100 mL) and the mixture extracted
with diethyl ether (2ϫ50 mL). The combined organic layers were
dried (MgSO4), concentrated and the residue was purified by col-
umn chromatography.
tions. The results contribute to a further understanding of
the various reaction modes. This helps to make such trans-
formations predictable and thus applicable in the synthesis
of multifunctional molecules with the desired skeletons.
General Procedure for Converting a Tetrahydropyranyloxy Group
Into a Bromine Substituent (GP3):[9] Bromine (60 mmol) was added
dropwise at –20 °C to a solution of triphenylphosphane (60 mmol)
in dichloromethane (150 mL). After stirring at –20 °C for 30 min,
the respective tetrahydropyranyl ether (27.0 mmol) was added to
the colorless suspension of the triphenylphosphane–bromine com-
plex, and stirring was continued at ambient temperature for 20 h.
Water was then poured into the reaction mixture, the two layers
were separated, and the aqueous layer was extracted with dichloro-
methane (100 mL). The combined organic layers were dried
(MgSO4), concentrated, and the resulting residue was purified by
column chromatography.
Experimental Section
1
General Remarks: H NMR spectra were recorded on Bruker AM
250 (250 MHz), and AX 300 (300 MHz) instruments at ambient
temperature for CDCl3 or C6D6 solutions with tetramethylsilane (δ
= 0.00 ppm) as an internal standard. The line positions or centers
of multiplets are given in ppm (δ) and the coupling constants (J)
are reported as absolute values in Hertz (Hz). Abbreviations for
the signal multiplicities: s (singlet), bs (broad singlet), d (doublet),
t (triplet), q (quartet), dd (doublet of doublets), ddd (doublet of
doublets of doublets), dt (doublet of triplets), tt (triplet of triplets),
dq (doublet of quartets), tq (triplet of quartets), m (multiplet), mc
(centered multiplet). 13C NMR spectra were recorded on a Bruker
AM 250 (62.5 MHz) instrument at ambient temperature for CDCl3
solutions, with δ (CDCl3) = 77.0 as an internal standard. When
signals could not be assigned unambiguously, the potentially corre-
sponding atoms concerned are marked with an asterisk (*). The
multiplicities of 13C NMR signals were determined with the help
of DEPT (Distortionless Enhancement by Polarization Transfer)
measurements and are designated as follows: CH3, CH = (+), CH2
= (–), quaternary C = (Cquat). Infrared spectra were recorded with
a Bruker FT-IR spectrometer IFS 66. Mass spectra were recorded
with Finnigan MAT CH 7 and MAT 731 spectrometers using elec-
tron impact ionization at 70 eV or direct chemical ionization with
NH3 as reactant gas. High-resolution mass spectra (HRMS) were
recorded with a Finnigan MAT 311 or an INCOS 50 with Varian
34000 (GC–MS) instrument using preselected ion peak matching at
R ≈ 10000 to be within Ϯ2 ppm. Microanalysis: Mikroanalytisches
Laboratorium des Instituts für Organische und Biomolekulare
Chemie der Georg-August-Universität Göttingen. Column
chromatography: Merck Silica Gel 60 (0.063–0.200 mm). Thin layer
chromatography: Macherey–Nagel Alugram G/UV254 0.25 mm sil-
ica gel-coated sheets with fluorescent indicator. Developer: molyb-
denumphosphoric acid solution (10% in ethanol). All operations
were performed under a nitrogen or an argon atmosphere. Solvents
were purified and dried according to conventional methods. The
following abbreviations are used: DME = 1,2-dimethoxyethane,
Et2O = diethyl ether, HMPA = hexamethylphosphorictriamide,
DMF = dimethylformamide, PE = light petroleum, b.p. 40–50 °C.
General Procedure for Coupling a 2-Bromoalkenyne with an Alde-
hyde (GP4): To a solution of the respective 2-bromoalkenyne
(1.0 mmol) in THF (15 mL) was added dropwise at –78 °C n-butyl-
lithium (24.0 mmol, hexane solution). After stirring for 30 min, the
respective aldehyde (1.05 mmol) was added, and stirring was con-
tinued at –78 °C for 30 min. After warming the mixture to –10 °C,
methyl iodide (1 mmol) and DMSO (10 mL) were added, and stir-
ring was continued at 0 °C for 2 h. The reaction mixture was then
diluted with water (20 mL), the two layers were separated, and the
aqueous layer was extracted with diethyl ether (2ϫ30 mL). The
combined organic layers were washed with conc. sodium chloride
solution (20 mL), dried (MgSO4), and concentrated. The resulting
residue was purified by column chromatography.
9-Bromo-1-nonen-6-yne (6): The preparation of 2-(8Ј-nonen-3Ј-yn-
yloxy)tetrahydro-2H-pyran from 5 and 4 with the use of sodium
amide in liquid ammonia and DMSO has been reported in the
literature.[12] Alternatively, it can be prepared according to GP(1)
by adding dropwise at –78 °C, n-butyllithium (26.3 mL, 42.0 mmol,
1.6  in hexane) to a solution of 2-(3Ј-butynyloxy)tetrahydro-2H-
pyran (4) (6.16 g, 40 mmol) in THF (80 mL). After stirring for
30 min, 5-bromo-1-pentene (5) (5.96 g, 40 mmol) and HMPA
(7.9 mL) were added, and stirring was continued at –78 °C for
30 min and at ambient temperature for 6 h. Work-up provided
8.90 g (100%) of 2-(8Ј-nonen-3Ј-ynyloxy)tetrahydro-2H-pyran as a
colorless liquid. Without any further purification, the latter com-
pound (8.90 g, 40 mmol) was added at –20 °C to a colorless suspen-
sion of triphenylphosphane–bromine complex formed by adding
dropwise at –20 °C bromine (16.0 g, 100 mmol) to a solution of
triphenylphosphane (26.2 g, 100 mmol) in dichloromethane
(240 mL). After stirring at ambient temperature for 20 h, work-up
as described in GP3, the resulting residue was purified by column
chromatography (250 g of silica gel, column 6ϫ 60 cm, pentane) to
General Procedure for Alkylating Alkynes with Alkyl Bromides
(GP1): To a solution of the respective alkyne (22.0 mmol) in THF
(50 mL) was added dropwise at –78 °C n-butyllithium (24.0 mmol,
hexane solution). After stirring at this temperature for 30 min, the
respective alkyl bromide (22.0 mmol) and HMPA (4.40 mL,
25 mmol) were added, and stirring was continued at –78 °C for 1 h
and then at ambient temperature for 6 h. The reaction mixture was
then diluted with water (50 mL) and the mixture extracted with
diethyl ether (3ϫ50 mL). The combined organic layers were dried
(MgSO4), concentrated, and the residue was purified by column
chromatography.
1
afford 4.52 g (56%) of 6 as a colorless liquid. Rf (PE) = 0.48. H
NMR (250 MHz, CDCl3): δ = 1.61 (tt, 3J = 7.3, 3J = 7.3 Hz, 2
3
5
H,4-H), 2.16 [m, 4 H, 3(5)-H], 2.71 (tt, J = 7.3, J = 2.3 Hz, 2 H,
8-H), 3.41 (t, 3J = 7.3 Hz, 2 H, 9-H), 4.99 (dt, 3J = 10.1, 4J =
1.0 Hz, 1 H, 1-H), 5.06 (dt, 3J = 17.5, J = 1.5 Hz, 1 H, 1-H), 5.77
4
(m, 1 H, 2-H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 18.03 (C-
5), 23.29 (C-8), 27.89 (C-4), 30.37 (C-9), 32.69 (C-3), 77.17 (C-6),
82.18 (C-7), 115.08 (C-1), 137.86 (C-2) ppm.
General Procedure for Alkylating Dialkyl Malonates with Alkyl Bro-
mides (GP2): The dialkyl malonate (55.0 mmol) was added drop-
wise at room temperature to a suspension of sodium hydride
(1.44 g, 60 mmol, oil suspension) in DME, DMF, or DMSO
(150 mL). The resulting clear solution was then transferred into a
solution of the respective alkyl halide (55.0 mmol) in DME, DMF,
or DMSO (20 mL). After stirring from 2 h to 2 d, the reaction mix-
Dimethyl 2-(8Ј-Nonen-3Ј-ynyl)malonate (7): Following GP2, di-
methyl malonate (2.64 g, 20 mmol) was added dropwise at room
temperature to a mixture of sodium hydride (0.88 g, 22 mmol, 60%
oil suspension) and anhydrous DMF (50 mL). The resulting clear
solution was transferred into a solution of 9-bromo-1-nonen-6-yne
(6) (3.71 g, 18.5 mmol) in DMF (20 mL). After stirring for 2 d and
4692
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4687–4699

Palladium-Catalyzed Oligocyclizations
work-up, the residue was purified by column chromatography (80 g
Diethyl 2-(4Ј-Pentynyl)malonate (13):[13] Following GP2, diethyl
malonate (8.0 g, 50 mmol) was added dropwise at room tempera-
ture to a solution of sodium hydride (2.2 g, 55 mmol, 60% oil sus-
pension) in anhydrous DMSO (100 mL). The resulting clear solu-
tion was transferred into a solution of 5-bromo-1-pentyne (7.35 g,
of silica gel, column 2.5ϫ 40 cm, PE/Et2O, 15:1) to afford 3.35 g
1
(72%) of 7 as a colorless oil. Rf (PE/Et2O, 15:1) = 0.25. H NMR
3
3
(250 MHz, CDCl3): δ = 1.54 (tt, J = 7.2, J = 7.2 Hz, 2 H, 6Ј-H),
3
2.00–2.25 [m, 8 H, 1Ј(2Ј,5Ј,7Ј)-H], 3.60 (t, J = 7.4 Hz, 1 H, 2-H),
3.72 (s, 6 H, OCH3), 4.93 (dt, J = 10.1, J = 1.0 Hz, 1 H, 9Ј-H), 50 mmol) in DMSO (20 mL). After stirring for 2 d and work-up,
3
4
3
4
5.00 (dt, J = 17.2, J = 1.4 Hz, 1 H, 9Ј-H), 5.76 (mc, 1 H, 8Ј-H)
the resulting residue was purified by column chromatography
(150 g of silica gel, column 5ϫ 40 cm, PE/Et2O, 15:1) to afford
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 16.68 (C-2Ј), 18.02 (C-
5Ј), 27.99 (C-6Ј*), 28.03 (C-1Ј*), 32.71 (C-7Ј), 50.20 (C-2), 52.51 (2 6.89 g (61%) of 13 as a colorless liquid. Rf (PE/Et2O, 10:1) = 0.31.
OCH3), 78.03 (C-3Ј**), 81.45 (C-4Ј**), 114.98 (C-9Ј), 137.91 (C- 1H NMR (250 MHz, CDCl3): δ = 1.24 (t, 3J = 7.1 Hz, 6 H,
8Ј), 169.54 (2 C=O) ppm. MS (DCI, NH3): m/z (%) = 522 (100)
OCH2CH3), 1.53 (mc, 2 H, 2Ј-H), 1.97 [m, 3 H, 1Ј(5Ј)-H], 2.16 (dt,
4
3
[2M + NH4+], 270 (10) [M + NH4+], 235 (18).
3J = 7.0, J = 2.6 Hz, 2 H, 3Ј-H), 3.42 (t, J = 7.0 Hz, 1 H, 2-H),
4.18 (m, 4 H, OCH2) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
13.98 (OCH3CH3), 18.05 (C-3Ј), 26.03 (CH2), 27.65 (CH2), 51.45
(C-2), 61.30 (OCH2), 68.82 (C-5Ј), 83.35 (C-4Ј), 169.16 (C=O) ppm.
Dimethyl 2-Bromotrideca-1,12-diene-7-yne-4,4-dicarboxylate (8):
Following GP2, to a suspension of sodium hydride (0.6 g, 15 mmol,
60% oil suspension) in DME (25 mL) was added dropwise at room
temperature dimethyl 2-(8Ј-nonen-3Ј-ynyl)malonate (7) (3.35 g,
13.3 mmol). After stirring for 30 min, 2,3-dibromopropene (3.0 g,
15.0 mmol) was added, and stirring was continued for 12 h. After
work-up, the residue was purified by column chromatography (80 g
of flash silica gel, column 2.5ϫ 40 cm, PE/Et2O, 15:1) to afford
4.0 g (81%) of 8 as a colorless oil. Rf (PE/Et2O, 15:1) = 0.29. IR
Diethyl 2-(2Ј-Bromoallyl)-2-(4ЈЈ-pentynyl)malonate (14): Following
GP2, to a suspension of sodium hydride (0.88 g, 22 mmol, 60% oil
suspension) in DME (40 mL) was added dropwise at room tem-
perature diethyl 2-(4Ј-pentynyl)malonate (13) (4.51 g, 20.0 mmol).
After stirring for 30 min, 2,3-dibromopropene (4.40 g, 22.0 mmol)
was added, and stirring was continued for 2 h. After work-up, the
residue was purified by column chromatography (80 g of silica gel,
column 2.5ϫ 50 cm, PE/Et2O, 20:1) to afford 4.06 g (60%) of 14
(film): ν = 3076 , 2950 (CH), 2842, 1737 (C=O), 1641, 1625 (C=C),
˜
1277, 1245, 1212, 1154, 1085, 1015, 913 cm–1. 1H NMR (250 MHz,
as a colorless oil. R (PE/Et O, 10:1) = 0.35. IR (film): ν = 3288
˜
f
2
3
3
CDCl3): δ = 1.40 (tt, J = 7.2, J = 7.2 Hz, 2 H, 10-H), 2.05–2.14
(alkyne), 2980 (CH), 1732 (C=O), 1626 (C=C), 1446, 1368, 1278,
1181, 1095, 1026, 902, 858, 643 cm–1. 1H NMR (250 MHz, CDCl3):
δ = 1.24 (t, 3J = 7.1 Hz, 6 H, OCH2CH3), 1.40 (m, 2 H, 2ЈЈ-H),
[m, 8 H, 5(6,9,11)-H], 3.15 (s, 2 H, 3-H), 3.71 (s, 6 H, OCH3), 4.95
4
(dt, 3J = 10.3, J = 1.0 Hz, 1 H, 13-H), 4.99 (dt, 3J = 17.1, 4J =
2
2
1.5 Hz, 1 H, 13-H), 5.57 (d, J = 1.6 Hz, 1 H, 1-H), 5.67 (d, J =
1.6 Hz, 1 H, 1-H), 5.76 (mc, 1 H, 12-H) ppm. 13C NMR (62.9 MHz,
CDCl3, DEPT): δ = 14.25 (–, C-6), 18.12 (–, C-9), 28.01 (–, C-10),
31.13 (–, C-5), 32.77 (–, C-11), 43.16 (–, C-3), 52.72 (+, 2 OCH3),
56.42 (Cquat, C-4), 78.52 (Cquat, C-7*), 80.63 (Cquat, C-8*), 115.00
(–, C-13), 122.06 (–, C-1),126.82 (Cquat, C-2), 137.94 (+, C-12),
170.53 (Cquat, 2 C=O) ppm. MS (DCI, NH3): m/z = 391/390/389/
388 (18:100:18:91) [M + NH4+]. C17H23BrO4 (371.3): calcd. C
55.00, H 6.24; found C 55.25, H 6.32.
4
3
1.93 (t, J = 2.6 Hz, 1 H, 5ЈЈ-H), 2.08 (m, 2 H, 1ЈЈ-H), 2.18 (dt, J
4
= 7.0, J = 2.6 Hz, 2 H, 3ЈЈ-H), 3.13 (s, 2 H, 1Ј-H), 4.17 (m, 4 H,
OCH2), 5.55 (d, 2J = 1.8 Hz, 1 H, 3Ј-H), 5.64 (m, 1 H, 3Ј-H) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 13.94 (2 OCH2CH3), 18.50 (C-
3ЈЈ), 23.28 (C-2ЈЈ), 30.51 (C-1ЈЈ), 42.78 (C-1Ј), 56.68 (C-2), 61.54 (2
OCH2), 68.76 (C-5ЈЈ), 83.46 (C-4ЈЈ), 121.73 (C-3Ј), 127.09 (C-2Ј),
170.33 (2 C=O) ppm. MS (DCI, NH3): m/z (%) = 365/364/363/362
(20:100:20:92) [M + NH4+].
Diethyl 2-Bromo-11,11-dimethyl-10-hydroxytetradeca-1,13-dien-8-
yne-4,4-dicarboxylate (16): n-Butyllithium (3.65 mL, 8.5 mmol,
2.33  in hexane) was added dropwise at –78 °C to a solution of
diethyl 2-(2Ј-bromoallyl)-2-(4ЈЈ-pentynyl)malonate (14) (2.76 g,
8.0 mmol) in THF (80 mL). After stirring at –78 °C for 30 min, 2,2-
dimethyl-4-pentenal (15) (1.01 g, 9.0 mmol) was added, and stirring
was continued at this temperature for 30 min. The reaction was
then quenched with water (10 mL), and the aqueous layer was ex-
tracted with Et2O (2ϫ30 mL). The combined organic layers were
dried (MgSO4), concentrated, and the residue was purified by col-
umn chromatography (50 g of flash silica gel, column 2.5ϫ35 cm,
Diethyl 2-Bromo-8-methoxytrideca-1,12-dien-6-yne-4,4-dicarboxyl-
ate (11): Following GP4, n-butyllithium (0.53 mL, 1.0 mmol, 1.88 
in hexane) was added dropwise at –78 °C to a solution of 2-(2Ј-
bromoallyl)-2-(3ЈЈ-propynyl)malonate (9)[6d] (317 mg, 1 mmol) in
THF (15 mL). After stirring at –78 °C for 30 min, 5-hexenal
(98 mg, 1.0 mmol) was added, and stirring was continued at this
temperature for 30 min. The reaction mixture was warmed to
–10 °C and methyl iodide (142 mg, 1 mmol) as well as DMSO
(10 mL) were added. After stirring at 0 °C for 2 h and work-up, the
residue was purified by column chromatography (20 g of silica gel,
column 1.5ϫ 20 cm, PE/Et2O, 10:1) to furnish 300 mg (70%) of 11 PE/Et2O, 3:1) to furnish 1.46 g (40%) of 16 as a colorless oil. Rf
as a colorless oil. IR (film): ν = 3074 , 2980, 2921, 1736, 1430, 1289,
(PE/Et O, 3:1) = 0.23. IR (film): ν = 2973 (CH), 2934, 1734 (C=O),
˜
˜
2
1216, 1110, 1045, 900, 619 cm–1. 1H NMR (250 MHz, CDCl3): δ
1626 (C=C), 1461, 1286, 1236, 1036, 911, 855 cm–1. 1H NMR
3
= 1.23 (t, J = 7.1 Hz, 6 H, OCH2CH3), 1.50 (m, 2 H, 10-H), 1.62
(250 MHz, CDCl3): δ = 0.92 (s, 3 H, 11-CH3), 0.94 (s, 3 H, 11-
3
3
3
(m, 2 H, 9-H), 2.04 (dt, J = 7.0, J = 7.0 Hz, 2 H, 11-H), 2.96 (d,
CH3), 1.24 (t, J = 7.1 Hz, 6 H, OCH2CH3), 1.40 (m, 2 H, 6-H),
5J = 1.8 Hz, 2 H, 5-H), 3.26 (s, 2 H, 3-H), 3.32 (s, 3 H,OCH3), 3.89 1.82 (br. s, 1 H, OH), 2.09 [m, 4 H, 5(12)-H], 2.24 (dt, J = 6.9, J
3
5
3
2
5
(m, 1 H, 8-H), 4.21 (m, 4 H, OCH2CH3), 4.93 (dd, J = 10.1, J =
= 1.9 Hz, 2 H, 7-H), 3.14 (s, 2 H, 3-H), 4.02 (t, J = 1.8 Hz, 1 H,
1.9 Hz, 1 H, 13-H), 5.00 (dd, J = 17.0, J = 2.0 Hz, 1 H, 13-H), 10-H), 4.18 (q, 3J = 7.1 Hz, 4 H, OCH2), 5.07 (m, 2 H, 14-H), 5.55
3
2
5.59 (d, J = 1.4 Hz, 1 H, 1-H), 5.79 (d, 2J = 1.4 Hz, 1 H, 1-H),
(d, 2J = 1.6 Hz, 1 H, 1-H), 5.64 (d, 2J = 1.6 Hz, 1 H, 1-H), 5.81
2
5.82 (m, 1 H, 12-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): (mc, 1 H, 13-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ =
δ = 13.88 (+, 2 OCH2CH3), 22.45 (–, C-5), 24.42 (–, C-10), 33.30 13.94 (+, 2 OCH2CH3), 18.88 (–, C-7), 22.41 (+, 11-CH3), 22.61
(–, C-11), 35.16 (–, C-9), 42.79 (–, C-3), 56.14 (Cquat, C-4), 56.17 (+, 11-CH3), 23.47 (–, C-6), 30.81 (–, C-5), 38.61 (Cquat, C-11),
(+, OCH3), 61.83 (–, 2 OCH2), 71.05 (+, C-8), 80.47 (Cquat,C-6*), 42.69 (–, C-3*), 42.97 (–, C-12*), 56.79 (Cquat, C-4), 61.56 (–, 2
82.74 (Cquat, C-7*), 114.63 (–, C-13), 122.30 (–, C-1), 126.57
OCH2), 70.33 (+, C-10), 80.16 (Cquat, C-8), 85.50 (Cquat, C-9),
(Cquat,C-2), 138.34 (+, C-12), 169.03 (Cquat, 2 C=O) ppm. MS (EI,
117.50 (–, C-14), 121.67 (–, C-1), 127.20 (Cquat, C-2), 135.00 (+, C-
70 eV): m/z (%) = 349 (100) [M+ – Br], 327 (13), 285 (22), 243 (59), 13), 170.38 (Cquat, 2 C=O) ppm. MS (DCI, NH3): m/z (%) = 477/
206 (17), 178 (21), 119 (36), 91 (30), 81 (22), 55 (13), 41 (16).
476/475/474 (23:100:24:98) [M + NH4+].
Eur. J. Org. Chem. 2010, 4687–4699
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4693

S. Schweizer, W. M. Tokan, P. J. Parsons, A. de Meijere
Diethyl 2-Bromo-11,11-dimethyl-10-oxotetradeca-1,13-dien-8-yne- methyl iodide (852 mg, 6 mmol) and DMSO (50 mL) were added,
FULL PAPER
4,4-dicarboxylate (17): DMSO (0.56 g, 7.17 mmol) was added drop-
wise at –60 °C to a solution of oxalyl chloride (0.46 g, 3.62 mmol)
in dichloromethane (10 mL). After stirring for 20 min, diethyl
2-bromo-11,11-dimethyl-10-hydroxytetradeca-1,13-dien-8-yne-4,4-
dicarboxylate (16) (1.46 g, 3.19 mmol) was added slowly, and stir-
ring was continued at this temperature for 30 min. Triethylamine
(0.76 g, 7.51 mmol) was added, and the reaction mixture was
warmed to room temperature. The mixture was then diluted with
water (10 mL), the two phases separated, and the aqueous phase
was extracted with dichloromethane (3ϫ10 mL). The combined
organic phases were washed with ammonium chloride solution
(5 mL), sodium chloride solution (5 mL), dried (MgSO4) and con-
centrated. The residue was purified by column chromatography
(20 g of flash silica gel, column 1.0ϫ30 cm, PE/Et2O, 10:1) to fur-
nish 1.03 g (71%) of 17 as a colorless oil. Rf (PE/Et2O, 5:1) = 0.31.
and stirring was continued at 0 °C for 2 h. After work-up, the resi-
due was purified by column chromatography (25 g of flash silica
gel, column 1.5ϫ35 cm, PE/Et2O, 40:1) to furnish 1.68 g (85%) of
20 as a colorless oil. R (PE/Et O, 20:1) = 0.27. IR (film): ν = 3074 ,
˜
f
2
2929, 1640 (C=C), 1445, 1383, 1327, 1099, 916, 672 cm–1. 1H NMR
(250 MHz, CDCl3): δ = 0.91 (s, 3 H, 4-CH3), 0.93 (s, 3 H, 4-CH3),
3
3
1.81 (tt, J = 7, J = 6 Hz, 2 H, 9-H), 2.10 (m, 2 H, 3-H), 2.37 (dt,
5
3
3J = 6.9, J = 1.9 Hz, 2 H, 8-H), 3.36 (s, 3 H, OCH3), 3.54 (t, J =
6.3 Hz, 2 H, 10-H), 3.56 (m, 1 H, 5-H), 4.07 (dd, 4J = 1, 4J = 1 Hz,
2
4
2 H, 1Ј-H), 5.00 (m, 2 H, 1-H), 5.59 (dt, J = 1.6, J = 0.8 Hz, 1
H, 3Ј-H), 5.77 (mc, 1 H, 2-H), 5.89 (d, 2J = 1.6 Hz, 1 H, 3Ј-H)
ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 15.49 (–, C-8),
22.73 (+, 4-CH3), 23.12 (4-CH3), 28.89 (–, C-9), 38.22 (Cquat, C-4),
43.01 (–, C-3), 57.12 (+, OCH3), 68.83 (–, C-10), 74.93 (–, C-1Ј),
77.79 (Cquat, C-7), 79.25 (+, C-5), 86.29 (Cquat, C-6), 117.30 (–, C-
3Ј*), 117.37 (–, C-1*), 129.65 (Cquat, C-2Ј), 135.01 (+, C-2) ppm.
IR (film): ν = 2976 (CH), 2206, 1733 (C=O), 1668 (C=O), 1626
˜
(C=C), 1367, 1278, 1180, 1094, 1025, 917 cm–1. 1H NMR MS (70 eV, EI): m/z (%) = 316/315/314/313 (0.2:1:0.2:1) [M+
–
3
(250 MHz, CDCl3): δ = 1.14 (s, 6 H, 11-CH3), 1.24 (t, J = 7.2 Hz,
CH3], 248/247/246/245 (2:20:2:22), 209 (15) [M+ – C3H4Br], 177
6 H, OCH2CH3), 1.46 (m, 2 H, 6-H), 2.10 (mc, 2 H, 5-H), 2.31 (d, (24), 134 (22), 127 (27), 109 (60), 105 (57), 79 (68), 55 (96), 41 (100).
3
3J = 7.5 Hz, 2 H, 12-H), 2.41 (t, J = 7.0 Hz, 2 H, 7-H), 3.15 (s, 2 MS (DCI, NH3): m/z (%) = 349/348/347/346 (15:100:15:97) [M +
3
H, 3-H), 4.19 (q, J = 7.2 Hz, 4 H, OCH2), 5.05 (m, 2 H, 14-H),
5.55 (m, 1 H, 1-H), 5.65 (br. s, 1 H, 1-H), 5.70 (mc, 1 H, 13-H) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 13.92 (2 OCH2CH3), 19.13 (C-
7), 22.66 (C-6), 23.52 (2ϫ11-CH3), 30.77 (C-5), 42.90 (C-3*), 43.47
(C-12*), 47.86 (C-11), 56.67 (C-4), 61.63 (2 OCH2), 79.26 (C-8),
94.12 (C-9), 118.20 (C-14), 121.82 (C-1), 127.00 (C-2), 133.53 (C-
13), 170.17 (2 C=O), 193.41 (C-10) ppm. MS (DCI, NH3): m/z (%)
NH4+]. C16H25BrO2 (329.3): calcd. C 58.36, H 7.65; found. C 58.55,
H 7.50.
2-(9Ј-Decen-3Ј-ynyloxy)tetrahydro-2H-pyran (25): Following GP1,
to a solution of 2-(3Ј-butynyloxy)tetrahydro-2H-pyran (21) (1.54 g,
10.0 mmol) in THF (20 mL) was added dropwise at –78 °C n-butyl-
lithium (4.72 mL, 11.0 mmol, 2.33  in hexane). After stirring at
this temperature for 30 min, 6-bromo-1-hexene (24) (1.63 g,
10.0 mmol) and HMPA (1.9 mL, 11 mmol) were added, and stir-
ring was continued at –78 °C for 1 h and at ambient temperature
for 6 h. After work-up, the residue was purified by column
chromatography (60 g of silica gel, column 2.5ϫ40 cm, PE/Et2O,
20:1) to furnish 1.68 g (71%) of 25 as a colorless liquid. Rf (PE/
=
475/474/473/472 (23:100:22:91) [M +
NH4+]. C22H31BrO5
(455.4): calcd. C 58.03, H 6.86; found C 58.01, H 7.00.
5-(2Ј-Bromoallyloxy)-1-pentyne (19): 4-Pentyn-1-ol (18) (841 mg,
10.0 mmol), cetyltrimethylammonium bromide (CETAB) (182 mg,
0.5 mmol) and 2,3-dibromopropene (2.0 g, 10.0 mmol) were added
at ambient temperature to a two-phase mixture of dichloromethane
(15 mL) and aq. sodium hydroxide solution (50%, 15 mL). After
stirring vigorously at ambient temperature for 6 h, the reaction
mixture was diluted with water (50 mL) as well as dichloromethane
(50 mL), and the two layers were separated. The aqueous layer was
further extracted with dichloromethane (50 mL), the combined or-
ganic layers were washed with sodium chloride solution, dried
(MgSO4) and concentrated. The residue (10 mL) was treated with
diethyl ether (100 mL), and the separated CETAB was filtered off.
The ether was evaporated, and the residue was purified by column
chromatography (40 g of silica gel, column 2ϫ30 cm, pentane/
Et2O, 40:1) to offer 1.35 g (72%) of 19 as a colorless liquid. 1H
Et O, 10:1) = 0.33. IR (film): ν = 2936 (CH), 1641 (C=C), 1441,
˜
2
1353, 1261, 1201, 1123, 1082, 1035, 909, 870, 815 cm–1. H NMR
1
(250 MHz, CDCl3): δ = 1.40–1.92 [m, 10 H, 3 (4, 5, 6Ј, 7Ј)-H], 2.05
5
(m, 2 H, 5Ј-H), 2.16 (m, 2 H, 8Ј-H), 2.45 (tt, 3J = 7.2, J = 2.4 Hz,
3
2 H, 2Ј-H), 3.53 (m, 2 H, 6-H), 3.83 (m, 2 H, 1Ј-H), 4.64 (t, J =
3
3
3.1 Hz, 1 H, 2-H), 4.93 (d, J = 10.1 Hz, 1 H, 10Ј-H), 4.98 (d, J
= 17.3 Hz, 1 H, 10Ј-H), 5.79 (mc, 1 H, 9Ј-H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 18.56 (C-5Ј), 19.38 (THP-C), 20.18 (C-2Ј),
25.40 (THP-C), 27.97 (C-6Ј*), 28.36 (C-7Ј*), 30.53 (THP-C), 33.26
(C-8Ј), 62.13 (C-6), 66.17 (C-1Ј), 76.90 (C-3Ј), 81.31 (C-4Ј), 98.66
(C-2), 114.46 (C-10Ј), 138.68 (C-9Ј) ppm. MS (70 eV, EI): m/z (%)
= 235 (0.4) [M+ – H], 207 (0.3), 193 (0.3), 191 (0.6), 181 (1), 119
(8), 115 (10), 91 (15), 85 (100) [C5H9O+], 79 (11), 41 (21).
3
3
NMR (250 MHz, CDCl3): δ = 1.80 (tt, J = 7, J = 6 Hz, 2 H, 4-
4
3
4
H), 1.94 (t, J = 2.7 Hz, 1 H, 1-H), 2.31 (dt, J = 7.1, J = 2.7 Hz,
2-(10Ј-Undecen-4Ј-ynyloxy)tetrahydro-2H-pyran (26): Following
GP1, to a solution of 2-(4Ј-pentynyloxy)tetrahydro-2H-pyran (22)
(2.27 g, 13.5 mmol) in THF (30 mL) was added dropwise at –78 °C
n-butyllithium (8.54 mL, 14.0 mmol, 1.64  in hexane). After stir-
ring at this temperature for 30 min, 6-bromo-1-hexene (24) (2.45 g,
15.0 mmol) and HMPA (3.1 mL, 18.0 mmol) were added, and stir-
ring was continued at –78 °C for 1 h and at ambient temperature
for 6 h. After work-up, the residue was purified by column
chromatography (80 g of silica gel, column 2.5ϫ50 cm, PE/Et2O,
20:1) to furnish 3.54 g (82%) of 26 as a colorless liquid. Rf (PE/
2 H, 3-H), 3.55 (t, 3J = 6.1 Hz, 2 H, 5-H), 4.08 (dd, 4J = 1, J =
4
2
4
1 Hz, 2 H, 1Ј-H), 5.59 (dt, J = 1.6, J = 0.8 Hz,1 H, 3Ј-H), 5.90
(d, J = 1.6 Hz, 1 H, 3Ј-H) ppm. 13C NMR (62.9 MHz, CDCl3): δ
2
= 15.16 (C-3), 28.46 (C-4), 68.60 (C-5 + C-1Ј), 74.88 (C-1), 83.69
(C-2), 117.36 (C-2Ј), 129.56 (C-3Ј) ppm. MS(70 eV, EI): m/z (%) =
203 (0.4) [M+ + H], 201 (0.5) [M+ – H], 189 (0.8), 187 (0.8), 123
(35),122/121/120/119 (20:93:20:84) [C3H4Br+], 97 (53), 95 (56), 81
(56), 67 (59), 53 (44), 41 (100). MS (DCI, NH3): m/z (%) = 223/
222/221/220 (10:95:9:100) [M + NH4+].
10-(2Ј-Bromoallyloxy)-4,4-dimethyl-5-methoxy-1-decen-6-yne (20): Et O, 10:1) = 0.33. IR (film): ν = 2937 , 2866, 1441, 1354, 1138,
˜
2
Following GP4, n-butyllithium (2.79 mL, 6.5 mmol, 2.33  in hex- 1121, 1063, 1035, 992, 909, 816 cm–1. 1H NMR (250 MHz, CDCl3):
ane) was added dropwise at –78 °C to a solution of 5-(2Ј-bromo-
allyloxy)-1-pentyne (19) (1.12 g, 6.0 mmol) in THF (50 mL). After
stirring at –78 °C for 30 min, 2,2-dimethyl-4-pentenal (15) (0.73 g, H, 6-H), 3.82 (m, 2 H, 1Ј-H), 4.57 (br. s, 1 H, 2-H), 4.93 (d, J =
6.5 mmol) was added, and stirring was continued at this tempera-
ture for 30 min. The reaction mixture was then warmed to 0 °C,
δ = 1.44–1.62 [m, 10 H, 3 (4, 5, 7Ј, 8Ј)-H], 1.76 (m, 2 H, 2Ј-H), 2.04
(m, 2 H, 9Ј-H), 2.1 (m, 2 H, 6Ј-H), 2.27 (m, 2 H, 3Ј-H), 3.48 (m, 2
3
3
10.2 Hz, 1 H, 11Ј-H), 5.00 (d, J = 17.1 Hz, 1 H, 11Ј-H), 5.80 (mc,
1 H, 10Ј-H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 15.57 (C-3Ј),
4694
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4687–4699

Palladium-Catalyzed Oligocyclizations
18.53 (C-6Ј), 19.44 (THP-C), 25.43 (THP-C), 27.97 (C-7Ј*), 28.46 4*), 28.38 (C-5*), 31.81 (C-10**), 32.61 (C-11**), 33.22 (C-3),
(C-8Ј*), 29.20 (C-2Ј), 30.61 (THP-C), 33.23 (C-9Ј), 62.05 (THP-C), 77.97 (C-8), 81.25 (C-7), 114.49 (C-1), 138.64 (C-2) ppm. MS (DCI,
65.97 (C-1Ј), 79.47 (C-4Ј**), 80.25 (C-5Ј**), 98.66 (THP-C), 114.41 NH3): m/z (%) = 246 (1) [M + NH4+], 166 (19), 109 (100).
(C-11Ј), 138.67 (C-10Ј) ppm. MS (70 eV, EI): m/z (%) = 250 (0.2)
12-Bromo-1-dodecen-7-yne (30): Following GP3, bromine (5.6 g,
[M+], 249 (0.4) [M+ – H], 207 (0.5), 167 (8), 97 (8), 85 (100)
35.0 mmol) was added dropwise at –20 °C to a solution of tri-
phenylphosphane (9.18 g, 35.0 mmol) in dichloromethane (80 mL).
[C5H9O+], 67 (12), 41 (11).
2-(11Ј-Dodecen-5Ј-ynyloxy)tetrahydro-2H-pyran (27): Following
After stirring at –20 °C for 30 min, 2-(11Ј-dodecen-5Ј-ynyloxy)-
GP1, to a solution of 2-(5Ј-hexynyloxy)tetrahydro-2H-pyran (23) tetrahydro-2H-pyran (27) (4.0 g, 15.1 mmol) was added to the col-
(6.38 g, 35.0 mmol) in THF (80 mL) was added dropwise at –78 °C
n-butyllithium (24.5 mL, 37.0 mmol, 1.51  in hexane). After stir-
ring at this temperature for 30 min, 6-bromo-1-hexene (24) (5.71 g,
35.0 mmol) and HMPA (5.0 mL, 30.0 mmol) were added and stir-
ring was continued at –78 °C for 1 h and at ambient temperature
for 6 h. After work-up, the residue was purified by column
chromatography (200 g of silica gel, column 5ϫ40 cm, PE/Et2O,
20:1) to furnish 4.0 g (43%) of 27 as a colorless liquid. Rf (PE/
orless suspension of the triphenylphosphane–bromine complex,
and stirring was continued at ambient temperature for 20 h. After
work-up, the residue was purified by column chromatography (80 g
of silica gel, column 2.5ϫ40 cm, pentane) to furnish 1.84 g (50%)
of 29 as a colorless liquid. Rf (pentane) = 0.51. 1H NMR
3
3
(250 MHz, CDCl3): δ = 1.47 [m, 4 H, 4(5)-H], 1.64 (tt, J = 7, J
3
= 7 Hz, 2 H, 10-H), 1.96 (tt, 3J = 7, J = 7 Hz, 2 H, 11-H), 2.04
3
(m, 2 H, 3-H), 2.16 [m, 4 H, 6(9)-H], 3.43 (t, J = 6.8 Hz, 2 H, 12-
3
3
Et O, 10:1) = 0.38. IR (film): ν = 2937 (CH), 2864, 1441, 1353, H), 4.94 (d, J = 10 Hz, 1 H, 1-H), 4.99 (d, J = 17 Hz, 1 H, 1-H),
˜
2
1138, 1121, 1077, 1035, 991, 908, 869, 815 cm–1. 1H NMR 5.80 (mc, 1 H, 2-H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 17.88
(250 MHz, CDCl3): δ = 1.40–1.90 (m, 14 H) 2.00–2.25 [m, 6 H, (C-9), 18.52 (C-6), 27.39 (C-10*), 27.99 (C-5*), 28.43 (C-4*), 31.68
4Ј(7Ј, 9Ј)-H], 3.48 (m, 2 H, 6-H), 3.80 (m, 2 H, 1Ј-H), 4.55 (br. s, 1
H, 2-H), 4.93 (d, J = 10 Hz, 1 H, 12Ј-H), 5.00 (d, J = 17 Hz, 1 114.45 (C-1), 138.67 (C-2) ppm. MS (DCI, NH3): m/z (%) = 262/
(C-11**), 33.22 (C-3**), 33.37 (C-12**), 79.22 (C-7), 80.73 (C-8),
3
3
H, 12Ј-H), 5.80 (mc, 1 H, 11Ј-H) ppm. 13C NMR (62.9 MHz,
CDCl3): δ = 18.54 (C-4Ј, C-7Ј), 19.56 (THP-C), 25.43 (THP-C),
25.85 (C-3Ј), 27.98 (C-8Ј*), 28.48 (C-9Ј*), 28.85 (C-2Ј*), 30.67
(THP-C), 33.22 (C-10Ј), 62.21 (THP-C), 67.00 (C-1Ј), 79.90 (C-
5Ј**), 80.18 (C-6Ј**), 98.70 (THP-C), 114.39 (CЈ-12), 138.68 (C-
11Ј) ppm. MS (DCI, NH3): m/z (%) = 282 (45) [M + NH4+], 198
(26) [(M – C5H8O) + NH4+], 102 (100).
260 (100:90) [M + NH4+].
Diethyl 2-(9Ј-Decen-3Ј-ynyl)malonate (31): Following GP2, diethyl
malonate (3.68 g, 23.0 mmol) was added dropwise at room tem-
perature to a mixture of sodium hydride (1.0 g, 25.0 mmol, 60%
oil suspension) and anhydrous DMSO (50 mL). The resulting clear
solution was transferred into a solution of 10-bromo-1-decen-7-
yne (28) (3.32 g, 15.4 mmol) in DMSO (5.0 mL), and stirring was
10-Bromo-1-decen-7-yne (28): Following GP3, bromine (8.0 g, continued for 30 h. After work-up, the residue was purified by col-
50.0 mmol) was added dropwise at –20 °C to a solution of tri-
phenylphosphane (13.1 g, 50.0 mmol) in dichloromethane
(120 mL). After stirring at –20 °C for 30 min, 2-(9Ј-decen-3Ј-yn-
yloxy)tetrahydro-2H-pyran (25) (5.0 g, 21.2 mmol) was added to
the colorless suspension of the triphenylphosphane–bromine com-
plex, and stirring was continued at ambient temperature for 20 h.
After work-up, the residue was purified by column chromatography
(100 g of silica gel, column 2.5ϫ60 cm, pentane) to furnish 3.31 g
(73%) of 28 as a colorless liquid. Rf (pentane) = 0.49. 1H NMR
(250 MHz, CDCl3): δ = 1.50 [m, 4 H, 4(5)-H], 2.06 (m, 2 H, 3-H),
umn chromatography (120 g of silica gel, column 5ϫ25 cm, PE/
Et2O, 20:1) to afford 2.89 g (64%) of diethyl 2-(9Ј-decen-3-ynyl)-
malonate (31) as a colorless oil. Rf (PE/Et2O, 10:1) = 0.28. IR
(film): ν = 3076 (CH), 2979, 2934, 2858, 1734 (C=O), 1641 (C=C),
˜
1446, 1370, 1249, 1156, 1097, 1049, 915, 862 cm–1. 1H NMR
(250 MHz, CDCl3): δ = 1.26 (t, 3J = 7.1 Hz, 6 H, OCH2CH3), 1.48
[m, 4 H, 6Ј(7Ј)-H], 2.06 [m, 4 H, 1Ј(8Ј)-H], 2.16 (m, 2 H, 2Ј-H),
3
3
2.23 (m, 2 H, 5Ј-H), 3.41 (t, J = 7.4 Hz, 1 H, 2-H), 4.19 (q, J =
3
7.1 Hz, 4 H, OCH2), 4.94 (d, J = 10.1 Hz, 1 H, 10Ј-H), 5.00 (d,
3J = 17.1 Hz, 1 H, 10Ј-H), 5.79 (m, 1 H, 9Ј-H) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 14.01 (2 OCH2CH3), 16.69 (C-2Ј), 18.49
(C-5Ј), 27.94 (C-6Ј, C-7Ј), 28.32 (C-1Ј), 33.21 (C-8Ј), 50.61 (C-2),
3
5
2.17 (m, 2 H, 6-H), 2.71 (tt, J = 7.4, J = 2.3 Hz, 2 H, 9-H), 3.41
3
3
(t, J = 7.4 Hz, 2 H, 10-H), 4.94 (d, J = 10.2 Hz, 1 H, 1-H), 5.01
(d, 3J = 17.5 Hz, 1 H, 1-H), 5.77 (m, 1 H, 2-H) ppm. 13C NMR 61.34 (2 OCH2), 78.01 (C-3Ј*), 81.52 (C-4Ј*), 114.44 (C-10Ј),
(62.9 MHz, CDCl3): δ = 18.51 (C-6), 23.32 (C-9), 27.95 (C-4*), 138.63 (C-9Ј), 169.18 (2 C=O) ppm. MS (DCI, NH3): m/z (%) =
28.18 (C-5*), 30.34 (C-10), 33.21 (C-3), 77.00 (C-8**), 82.40 (C- 606 (25) [2M + NH4+], 312 (100) [M + NH4+].
7**), 114.51 (C-1), 138.61 (C-2) ppm.
Diethyl 2-(10Ј-Undecen-4Ј-ynyl)malonate (32): Following GP2, di-
11-Bromo-1-undecen-7-yne (29): Following GP3, bromine (5.6 g, ethyl malonate (1.81 g, 11.3 mmol) was added dropwise at room
35.0 mmol) was added dropwise at –20 °C to a solution of tri-
phenylphosphane (9.18 g, 35.0 mmol) in dichloromethane (80 mL).
After stirring at –20 °C for 30 min, 2-(10Ј-undecen-4Ј-ynyloxy)-
tetrahydro-2H-pyran (26) (3.81 g, 15.2 mmol) was added to the col-
orless suspension of the triphenylphosphane–bromine complex,
and stirring was continued at ambient temperature for 20 h. After
work-up, the residue was purified by column chromatography (80 g
of silica gel, column 2.5ϫ40 cm, pentane) to furnish 2.03 g (58%)
temperature to a mixture of sodium hydride (0.48 g, 12 mmol, 60%
oil suspension) and anhydrous DMF (15 mL). The clear solution
was transferred into a solution of 11-bromo-1-undecen-7-yne (29)
(2.03 g, 8.9 mmol) in DMF (5.0 mL), and stirring was continued
for 1 d. After work-up, the resulting residue was purified by column
chromatography (40 g of silica gel, column 2ϫ30 cm, PE/Et2O,
20:1) to afford 1.62 g (60%) of 32 as a colorless oil. Rf (PE/Et2O,
10:1) = 0.29. IR (film): ν = 3076 , 2933, 2860, 1734 (C=O), 1641
˜
of 29 as a colorless liquid. R (pentane) = 0.49. IR (film): ν = 3075 ,
(C=C), 1446, 1369, 1151, 1097, 1031, 865 cm–1. 1H NMR
(250 MHz, CDCl3): δ = 1.25 (t, 3J = 7.1 Hz, 6 H, OCH2CH3), 1.46
[m, 6 H, 2Ј(7Ј, 8Ј)-H], 2.0 [m, 4 H, 1Ј(9Ј)-H], 2.15 [m, 4 H, 3Ј(6Ј)-
˜
f
2930 (CH), 2857, 1641 (C=C), 1434, 1273, 1248, 994, 914, 651 (Br)
cm–1. 1H NMR (250 MHz, CDCl3): δ = 1.48 [m, 4 H, 4(5)-H], 1.99
3
3
3
(tt, J = 7, J = 7 Hz, 2 H, 10-H), 2.05 (m, 2 H, 3-H), 2.14 (tt, J
H], 3.33 (t, 3J = 7.6 Hz, 1 H, 2-H), 4.17 (q, 3J = 7.1 Hz, 4 H,
= 6.7, J = 2.4 Hz, 2 H, 6-H), 2.33 (tt, J = 6.8, J = 2.4 Hz, 2 H, OCH2), 4.93 (d, J = 10 Hz, 1 H, 11Ј-H), 4.98 (d, 3J = 17 Hz, 1 H,
5
3
5
3
9-H), 3.52 (t, J = 7 Hz, 2 H, 11-H), 4.94 (d, J = 10.1 Hz, 1 H, 1- 11Ј-H), 5.78 (mc, 1 H, 10Ј-H) ppm. 13C NMR (62.9 MHz, CDCl3):
3
3
H), 4.99 (d, J = 17.2 Hz, 1 H, 1-H), 5.80 (mc, 1 H, 2-H) ppm. 13C δ = 14.03 (2 OCH2CH3), 18.42 (C-3Ј*), 18.51 (C-6Ј*), 26.69 (CH2),
3
NMR (62.9 MHz, CDCl3): δ = 17.44 (C-9), 18.52 (C-6), 27.99 (C- 27.83 (CH2), 27.98 (CH2), 28.41 (CH2), 33.22 (C-9Ј), 51.56 (C-2),
Eur. J. Org. Chem. 2010, 4687–4699
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4695

S. Schweizer, W. M. Tokan, P. J. Parsons, A. de Meijere
FULL PAPER
61.28 (2 OCH2), 79.08 (C-4Ј*), 80.68 (C-5Ј*), 114.41 (C-11Ј), NMR (250 MHz, CDCl3): δ = 1.24 (t, 3J = 7.1 Hz, 6 H,
138.68 (C-10Ј), 169.32 (2 C=O) ppm. MS(70 eV, EI): m/z (%) = 308 OCH2CH3), 1.46 [m, 6 H, 6(11,12)-H], 2.03–2.18 [m, 8 H,
(0.3) [M+], 189 (55), 173 (46), 161 (62), 160 (100) [M+ – (C6H10O4 5(7,10,13)-H], 3.14 (s, 2 H, 3-H), 4.19 (q, 3J = 7.1 Hz, 4 H, OCH2),
3
3
+ 2 H)], 148 (73), 133 (65), 119 (76), 93 (64), 91 (83), 80 (60), 79
(89), 67 (50), 55 (37), 41 (56).
4.92 (d, J = 10.1 Hz, 1 H, 15-H), 4.98 (d, J = 16.9 Hz, 1 H, 15-
2
2
H), 5.55 (d, J = 2 Hz, 1 H, 1-H), 5.65 (d, J = 2 Hz, 1 H, 1-H),
5.79 (mc, 1 H, 14-H) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 13.95
(2 OCH2CH3), 18.53 (C-7*), 18.89 (C-10*), 23.87 (C-6), 28.01 (C-
11**), 28.43 (C-12**), 30.60 (C-5), 33.24 (C-13), 42.74 (C-3), 56.71
(C-4), 61.50 (2 OCH2), 79.17 (C-8***), 80.58 (C-9***), 114.44 (C-
15), 121.63 (C-1), 127.23 (C-2), 138.67 (C-14), 170.44 (2 C=O)
ppm. MS (DCI, NH3): m/z (%) = 447/446/445/444 (22:100:21:92)
[M + NH4+]. C21H31BrO4 (427.4): calcd. C 59.02, H 7.31; found C
59.17, H 7.34.
Diethyl 2-(11Ј-Dodecen-5Ј-ynyl)malonate (33): Following GP2, di-
ethyl malonate (1.36 g, 8.5 mmol) was added dropwise at room
temperature to a mixture of sodium hydride (0.34 g, 8.5 mmol, 60%
oil suspension) and anhydrous DMF (10 mL). The resulting clear
solution was transferred into a solution of 12-bromo-1-dodecen-
7-yne (30) (1.84 g, 7.6 mmol) in DMF (5.0 mL), and stirring was
continued for 1 d. After work-up, the residue was purified by col-
umn chromatography (40 g of silica gel, column 2ϫ30 cm, PE/
Et2O, 20:1) to afford 1.87 g (77%) of 33 as a colorless oil. Rf (PE/
Diethyl 2-Bromohexadeca-1,15-dien-9-yne-4,4-dicarboxylate (36):
Following GP2, diethyl 2-(11Ј-dodecen-5Ј-ynyl)malonate (33)
(1.87 g, 5.8 mmol) was added dropwise at room temperature to a
mixture of sodium hydride (0.24 g, 6.0 mmol, 60% oil suspension)
and DME (12 mL). After stirring for 30 min, 2,3-dibromopropene
(1.4 g, 7.0 mmol) was added, and stirring was continued for 12 h.
After work-up, the residue was purified by column chromatography
(40 g of flash silica gel, column 2.0ϫ30 cm, PE/Et2O, 20:1) to af-
ford 1.70 g (66%) of 36 as a colorless oil. Rf (PE/Et2O, 10:1) =
Et O, 10:1) = 0.26. IR (film): ν = 2980 , 2931 (CH), 1733 (C=O),
˜
2
1641 (C=C), 1457, 1369, 1194, 1110, 1030, 853 cm–1. 1H NMR
(250 MHz, CDCl3): δ = 1.24 (t, 3J = 7.0 Hz, 6 H, OCH2CH3), 1.45
[m, 8 H, 2Ј(3Ј, 8Ј, 9Ј)-H], 1.87 (dt, J = 7.6, J = 7.6 Hz, 2 H, 1Ј-
H), 1.99–2.15 [m, 6 H, 4Ј(7Ј, 10Ј)-H], 3.29 (t, J = 7.6 Hz, 1 H, 2-
3
3
3
H), 4.16 (q, 3J = 7.0 Hz, 4 H, OCH2), 4.92 (d, 3J = 10 Hz, 1 H,
12Ј-H), 4.98 (d, 3J = 17 Hz, 1 H, 12Ј-H), 5.83 (mc, 1 H, 11Ј-H) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 14.01 (2 OCH2CH3), 18.44 (C-
4Ј*), 18.50 (C-7Ј*), 26.45 (C-2Ј), 27.97 (CH2), 28.23 (CH2), 28.44
(CH2), 28.63 (CH2), 33.20 (C-10Ј), 51.88 (C-2), 61.22 (2 OCH2),
79.65 (C-5Ј**), 80.24 (C-6Ј**), 114.39 (C-12Ј), 138.65 (C-11Ј),
169.40 (2 C=O) ppm. MS (DCI, NH3): m/z (%) = 662 (10) [2M +
NH4+], 340 (100) [M + NH4+].
0.30. IR (film): ν = 2933 (CH), 2859, 1735 (C=O), 1626 (C=C),
˜
1463, 1282, 1237, 1175, 1097, 1036, 911, 859 cm–1. 1H NMR
(250 MHz, CDCl3): δ = 1.27 (t, 3J = 7.1 Hz, 6 H, OCH2CH3), 1.45
[m, 8 H, 6(7,12,13)-H], 1.94–2.15 [m, 8 H, 5(8,11,14)-H], 3.16 (s, 2
3
3
H, 3-H), 4.17 (q, J = 7.1 Hz, 4 H, OCH2), 4.93 (d, J = 11 Hz, 1
H, 16-H), 4.98 (d, 3J = 17 Hz, 1 H, 16-H), 5.55 (d, J = 2 Hz, 1 H,
2
1-H), 5.64 (d, 2J = 2 Hz, 1 H, 1-H), 5.78 (mc, 1 H, 15-H) ppm. 13
C
Diethyl 2-Bromotetradeca-1,13-diene-7-yne-4,4-dicarboxylate (34):
Following GP2, diethyl 2-(9Ј-decen-3Ј-ynyl)malonate (31) (2.89 g,
9.82 mmol) was added dropwise at room temperature to a mixture
of sodium hydride (0.47 g, 11.7 mmol, 60% oil suspension) and
DME (20 mL). After stirring for 30 min, 2,3-dibromopropene
(3.0 g, 15.0 mmol) was added, and stirring was continued for 5 h.
After work-up, the residue was purified by column chromatography
(80 g of flash silica gel, column 2.5ϫ40 cm, PE/Et2O, 30:1) to af-
ford 3.35 g (83%) of 34 as a colorless oil. Rf (PE/Et2O, 20:1) =
NMR (62.9 MHz, CDCl3): δ = 13.95 (2 OCH2CH3), 18.42 (C-8*),
18.53 (C-11*), 22.99 (C-6), 28.02 (C-7**), 28.49 (C-12**), 29.09 (C-
13**), 30.63 (C-5), 33.23 (C-14), 42.60 (C-3), 56.87 (C-4), 61.45 (2
OCH2), 79.69 (C-9***), 80.23 (C-10***), 114.45 (C-16), 121.55 (C-
1), 127.38 (C-2), 138.64 (C-15), 170.54 (2 C=O) ppm. MS (DCI,
NH3): m/z (%) = 903/902/901/900/899/898 (23:50:38:80:22:40) [2M
+ NH4+], 461/460/459/458 (22:100:22:99) [M + NH4+]. C22H33BrO4
(441.4): calcd. C 59.86, H 7.54; found C 59.58, H 7.96.
0.26. IR (film): ν = 2975 (CH), 2934, 2859, 1733 (C=O), 1625
˜
General Procedure for Palladium-Catalyzed Oligocyclizations of 2-
Bromoalka-1,(n+m+1)-dien-(n+1)-ynes Initiated by a Heck-Type
Reaction (GP5)
(C=C), 1446, 1368, 1262, 1186, 1097, 1024, 908, 861, 803 cm–1. 1H
NMR (250 MHz, CDCl3): δ = 1.25 (t, 3J = 7.1 Hz, 6 H,
OCH2CH3), 1.45 [m, 4 H, 10(11)-H], 2.11 [m, 6 H, 5(6,12)-H], 2.20
(m, 2 H, 9-H), 3.15 (s, 2 H, 3-H), 4.18 (q, 3J = 7.1 Hz, 4 H, OCH2),
Method A: Palladium acetate (0.1 equiv.) is added at 60 °C to a
degassed mixture, placed in a Pyrex® bottle with a screw cap, of
triphenylphosphane (0.25 equiv.), potassium or silver carbonate
(2.5 equiv.), and the respective 2-bromoalka-1,(n+m+1)-dien-(n+1)-
yne (1 equiv.) in acetonitrile. After stirring at 60 °C for 1 to 12 h,
the reaction mixture is allowed to cool to room temperature, fil-
tered through a layer each of Celite® and of charcoal, then concen-
trated. The residue is purified by column chromatography.
3
3
4.93 (d, J = 10.0 Hz, 1 H, 14-H), 4.99 (d, J = 17.2 Hz, 1 H, 14-
2
2
H), 5.58 (d, J = 1.6 Hz, 1 H, 1-H), 5.67 (d, J = 1.7 Hz, 1 H, 1-
H), 5.78 (mc, 1 H, 13-H) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
14.92 (2 OCH2CH3), 14.20 (C-6), 18.57 (C-9), 28.00 (C-10*), 28.31
(C-11*), 31.01 (C-5), 33.22 (C-12), 42.94 (C-3), 56.43 (C-4), 61.61
(2 OCH2), 78.49 (C-7**), 80.70 (C-8**), 114.45 (C-14), 121.86 (C-
1), 127.06 (C-2), 138.65 (C-13), 170.10 (2 C=O) ppm. MS (DCI,
NH3): m/z (%) = 846/844/842 (9:18:7) [2M + NH4+], 433/432/431/
430 (18:100:18:96) [M + NH4+]. C20H29BrO4 (413.4): calcd. C
58.11, H 7.07; found C 58.06, H 7.22.
Method B: Palladium acetate (0.1 equiv.) is added at 80 °C to a
degassed mixture, placed in a Pyrex® bottle with a screw cap, of
triphenylphosphane (0.25 equiv.), sodium formate (1.2 equiv.) or
silver carbonate (3.0 equiv.), and of the respective precursor 2-bro-
moalka-1,(n+m+1)-dien-(n+1)-yne (1 equiv.) in DMF. After stir-
ring at 80 °C from 1 to 12 h, the reaction mixture is poured into
water (30 mL) and the mixture extracted with diethyl ether
(3ϫ20 mL). The combined ether layers are dried (MgSO4), concen-
trated, and the residue is purified by column chromatography.
Diethyl 2-Bromopentadeca-1,14-dien-8-yne-4,4-dicarboxylate (35):
Following GP2, diethyl 2-(10Ј-undecen-4Ј-ynyl)malonate (32)
(1.62 g, 5.25 mmol) was added dropwise at room temperature to a
mixture of sodium hydride (0.22 g, 5.5 mmol, 60% oil suspension)
and DME (10 mL). After stirring for 30 min, 2,3-dibromopropene
(1.2 g, 6.0 mmol) was added, and stirring was continued for 12 h.
After work-up, the residue was purified by column chromatography
(40 g of flash silica gel, column 2.0ϫ30 cm, PE/Et2O, 25:1) to af-
Palladium-Catalyzed Oligocyclization of Dimethyl 2-Bromotrideca-
1,12-diene-7-yne-4,4-dicarboxylate (8): Following GP5, method A,
ford 1.71 g (76%) of 34 as a colorless oil. Rf (PE/Et2O, 10:1) = dimethyl 2-bromotrideca-1,12-diene-7-yne-4,4-dicarboxylate (8)
0.32. IR (film): ν = 3075 , 2978, 2934, 2860, 1733 (C=O), 1626
(371 mg, 1.0 mmol) upon treatment at 80 °C with palladium acetate
(22 mg, 0.10 mmol), triphenylphosphane (66 mg, 0.25 mmol) and
˜
(C=C), 1445, 1367, 1277, 1180, 1095, 1038, 910, 859 cm–1. 1H
4696
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4687–4699

Palladium-Catalyzed Oligocyclizations
silver carbonate (828 mg, 3.0 mmol) in acetonitrile (10 mL), after
16 h, work-up and purification by column chromatography (20 g
of flash silica gel, column 1ϫ35 cm, PE/Et2O, 20:1), afforded the
following fractions:
Et2O, 5:1), afforded 124 mg (33%) of 40 as a colorless oil. Rf (PE/
Et O, 5:1) = 0.17. IR (film): ν = 2958 (CH), 2864, 1732 (C=O),
˜
2
1695 (C=O), 1639 (C=C), 1603, 1447, 1390, 1316, 1261, 1225, 1095
1
cm–1. 1035, 861, 799. H NMR (250 MHz, CDCl3): δ = 1.03 (s, 6
H, 4-CH3), 1.20 (m, 2 H, 13-H), 1.21 (t, 3J = 7.1 Hz, 6 H,
OCH2CH3), 1.59 (m, 2 H, 12-H), 2.15 (mc, 2 H, 14-H), 2.34 [m, 5
H, 5(7, 8)-H], 2.76 [m, 3 H, 5(10)-H], 4.10 (m, 4 H, OCH2) ppm.
13C NMR (62.9 MHz, CDCl3, DEPT): δ = 13.94 (+, 2 OCH2CH3),
22.29 (–, C-13), 25.27 (+, 2 4-CH3), 25.52 (–, C-8*), 26.80 (–, C-
Fraction I: 88 mg (30%) of dimethyl tricyclo[7.4.0.02,6]trideca-
1(9),2(6)-diene-11,11-dicarboxylate (37) as a colorless oil. Rf (PE/
Et O, 10:1) = 0.25. IR (film): ν = 3436 , 2978, 2869, 2086, 1635
˜
2
(C=O), 1383, 1350, 1124, 1077, 640 cm–1. 1H NMR (250 MHz,
3
3
CDCl3): δ = 1.84 (tt, J = 7, J = 7 Hz, 2 H, 4-H), 2.14 [m, 8 H,
7(8,12,13)-H], 2.30 [t, J = 7 Hz, 4 H, 3(5)-H], 2.55 (br. s, 2 H, 10-
7*), 30.68 (–, C-12), 36.96 (–, C-14), 38.68 (–, C-10), 44.25 (Cquat
,
3
C-4), 45.37 (–, C-5), 55.21 (Cquat, C-11), 61.05 (–, 2 OCH2), 131.84
(Cquat), 132.08 (Cquat), 133.81 (Cquat), 169.74 (Cquat, C-6), 171.56
(Cquat, 2 C=O), 210.22 (Cquat, C-14) ppm. MS (DCI, NH3): m/z
(%) = 766 (12) [2M + NH4+], 392 (100) [M + NH4+].
H), 3.70 (s, 6 H, OCH3) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
22.41 (C-4), 22.94 (C-13), 23.88 (C-8*), 27.84 (C-12), 29.16 (C-7*),
30.97 (C-3), 34.97 (C-10), 35.50 (C-5), 52.56 (OCH3), 52.63
(OCH3), 53.33 (C-4), 124.20, 124.91, 134.04, 134.33, 172.02 (2
C=O) ppm. MS (70 eV, EI): m/z (%) = 290 (9) [M+], 288 (8) [M+
–
Palladium-Catalyzed Oligocyclization of 10-(2Ј-Bromoallyloxy)-4,4-
dimethyl-5-methoxy-1-decen-6-yne (20): Following GP5, method B,
10-(2Ј-bromoallyloxy)-4,4-dimethyl-5-methoxy-1-decen-6-yne (20)
(329 mg, 1.0 mmol) upon treatment at 80 °C with palladium acetate
(22 mg, 0.10 mmol), triphenylphosphane (66 mg, 0.25 mmol) and
silver carbonate (828 mg, 3.0 mmol) in DMF (10 mL), after 5 d,
work-up and purification by column chromatography (20 g of flash
silica gel, column 1ϫ35 cm, PE/Et2O, 5:1), afforded 69 mg (48%)
of a 9:1 mixture of 41 and 42. Further two purifications by column
chromatography (20 g of flash silica gel, column 1ϫ35 cm, PE/
Et2O, 5:1) afforded 25 mg (17%) of pure 10-methoxy-9,9-dimethyl-
2,3,5,6,7,8,9,10-octahydro-1H-indeno[5,4-c]oxepine (41) as a color-
2 H], 230 (50), 229 (36), 228 (96), 169 (100), 141 (62), 129 (28), 115
(21), 59 (31).
Fraction II: 52 mg (18%) of dimethyl tricyclo[7.4.0.02,6]trideca-
1(9),2(6),7-triene-11,11-dicarboxylate (38) as a colorless oil. Rf (PE/
Et O, 10:1) = 0.21. IR (film): ν = 2951 , 2841, 1736 (C=O), 1484,
˜
2
1436, 1258, 1087, 1068, 1025, 807 cm–1. 1H NMR (300 MHz,
3
3
3
C6D6): δ = 1.77 (tt, J = 7.4, J = 7.4 Hz, 2 H, 4-H), 2.41 (t, J =
7 Hz, 2 H, 12-H), 2.46 (t, 3J = 7 Hz, 2 H, 5-H), 2.63 (t, 3J = 6.8 Hz,
3
2 H, 13-H), 2.69 (t, J = 7.4 Hz, 2 H, 3-H), 3.27 (s, 6 H, OCH3),
3
3
3.43 (br. s, 2 H, 10-H), 6.91 (d, J = 7.7 Hz, 1 H, 7-H), 6.96 (d, J
= 7.7 Hz, 1 H, 8-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT):
δ = 23.73 (–, C-13), 24.74 (-, C-4), 28.02 (–, C-12), 30.88 (–, C-5),
32.66 (–, C-3), 34.61 (C-10), 52.65 (+, 2 OCH3), 53.46 (Cquat, C-
11), 121.90 (+, C-8), 126.83 (+, C-7), 130.24 (Cquat), 130.55 (Cquat),
141.67 (Cquat), 142.45 (Cquat), 171 (Cquat, 2 C=O) ppm. MS (70 eV,
EI): m/z (%) = 288 (29) [M+], 228 (100), 169 (87), 141 (30). HRMS:
calcd. for C17H20O4 (288.3): 288.1361 (correct mass).
less oil. R (PE/Et O, 5:1) = 0.13. IR (film): ν = 2932 (CH), 1721
˜
f
2
(C=O), 1465, 1384, 1364, 1263, 1098, 1030, 736, 703 cm–1. 1H
NMR (250 MHz, CDCl3): δ = 1.06 (s, 3 H, 9-CH3), 1.12 (s, 3 H,
2
9-CH3), 1.84 (m, 2 H, 2-H), 1.95 (d, J = 17.1 Hz, 1 H, 8-H), 2.08
[m, 4 H, 6*(7*)-H], 2.36 (d, 2J = 17.1 Hz, 1 H, 8-H), 2.47 (m, 2 H,
2
1-H*), 3.34 (s, 3 H, OCH3), 3.79 (s, 1 H, 10-H), 3.82 (ddd, J = 6,
3J = 6, 3J = 3 Hz, 2 H, 3-H), 4.13 (br. s, 2 H, 5-H) ppm. 13C NMR
(62.9 MHz, CDCl3, DEPT): δ = 22.91 (+,9-CH3), 24.13 (–, C-6*),
26.54 (–, C-7*), 27.67 (–, C-2**), 28.61 (–, C-1**), 30.13 (+,9-CH3),
41.58 (Cquat, C-9), 49.58 (–, C-8), 57.58 (+, OCH3), 71.86 (–, C-
3***), 72.47 (–, C-5***), 92.53 (+, C-10), 131.06 (Cquat), 131.61
(Cquat), 135.09 (Cquat), 138.89 (Cquat) ppm. MS (70 eV, EI): m/z (%)
= 249 (17) [M+ + H], 248 (100) [M+], 216 (39), 201 (25), 173 (32),
162 (34), 159 (31), 145 (22). HRMS: calcd. for C16H24O2 (248.4):
248.1776 (correct mass).
Diethyl 13-Methoxytricyclo[7.4.0.02,6]trideca-1(9),2(6)-diene-4,4-di-
carboxylate (39): Following GP5, method A, diethyl 2-bromo-8-
methoxytrideca-1,12-dien-6-yne-4,4-dicarboxylate (11) (300 mg,
0.7 mmol) upon treatment at 80 °C with palladium acetate (8.0 mg,
0.036 mmol), triphenylphosphane (19 mg, 0.072 mmol) and silver
carbonate (580 mg, 2.10 mmol) in acetonitrile (10 mL), after 16 h,
work-up and purification by column chromatography (20 g of flash
silica gel, column 1.5ϫ20 cm, PE/Et2O, 10:1), afforded, in addition
to a complex mixture of inseparable products, 90 mg (37%) of 39
A mixture (44.0 mg) of 41 and 42 was added at ambient tempera-
ture into a dark-red solution of 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ) (46 mg, 0.20 mmol) in benzene (20 mL). Af-
ter stirring for 30 min, Et2O (20 mL) and sodium hydroxide solu-
tion (1%, 10 mL) were added. The two layers were separated, and
the aqueous layer was extracted with Et2O (3ϫ20 mL). The com-
bined organic layers were dried (MgSO4), concentrated, and the
resulting residue was purified by column chromatography (10 g of
flash silica gel, column 1ϫ15 cm, PE/Et2O, 5:1) to afford 40 mg
(92%) of pure 10-methoxy-9,9-dimethyl-2,3,5,8,9,10-hexahydro-
1H-indeno[5,4-c]oxepine (42) as a colorless oil. Rf (PE/Et2O, 5:1)
as a colorless oil. IR (film): ν = 2930 , 1733 (C=O), 1446, 1258,
˜
1
1185, 1096 (C–O), 862, 800 cm–1. H NMR (250 MHz, CDCl3): δ
= 1.27 (m, 6 H, OCH2CH3), 1.4–1.9 [m, 6 H, 10(11,12)-H], 2.07–
2.13 [m, 4 H, 7(8)-H], 2.9–3.2 [m, 4 H, 3(5)-H], 3.38 (s, 3 H, OCH3),
3.45 (m, 1 H, 13-H), 4.18 (m, 4 H, OCH2CH3) ppm. 13C NMR
(62.9 MHz, CDCl3, DEPT): δ = 14.03 (+, 2 OCH2CH3), 17.54 (–,
C-11), 23.05 (–, CH2), 25.89 (–, C-12), 29.50 (–, CH2), 30.30 (–,
CH2), 39.56 (–, C-3), 43.26 (–, C-5), 55.85 (+, OCH3), 58.74 (Cquat
C-4), 61.35 (–, OCH2), 61.42 (–, OCH2), 73.51 (+, C-13), 125.87
(Cquat,C-9), 130.72 (Cquat, C-6), 131.30 (Cquat, C-1), 134.28 (Cquat
,
,
C-2), 172.09 (Cquat, C=O), 172.69 (Cquat, C=O) ppm. MS (EI,
70 eV): m/z (%) = 348 (41) [M+], 316 (61) [M+ – CH3OH], 275 (19),
242 (100), 197 (12), 169 (61), 143 (20), 91 (15), 57 (13), 44 (19).
= 0.17. IR (film): ν = 3073 (CH), 2974, 2871, 1732 (C=O), 1626
˜
(C=C), 1446, 1367, 1278, 1181, 1029, 914 cm–1. 1H NMR
(250 MHz, CDCl3): δ = 1.00 (s, 3 H, 9-CH3), 1.26 (s, 3 H, 9-CH3),
2
2
Diethyl
4,4-Dimethy-3-oxotricyclo[7.5.0.02,6]tetradeca-1(9),2(6)- 1.83 (m, 2 H, 2-H), 2.49 (d, J = 15.6 Hz, 1 H, 8-H), 2.94 (d, J =
diene-11,11-dicarboxylate (40): Following GP5, method A, diethyl
2-bromo-11,11-dimethyl-10-oxotetradeca-1,13-dien-8-yne-4,4-di-
carboxylate (17) (455 mg, 1.0 mmol) upon treatment at 80 °C with
palladium acetate (22.0 mg, 0.10 mmol), triphenylphosphane
(66 mg, 0.25 mmol) and silver carbonate (828 mg, 3.0 mmol) in ace-
tonitrile (10 mL), after 4 d, work-up and purification by column
chromatography (20 g of flash silica gel, column 1.0ϫ35 cm, PE/
15.6 Hz, 1 H, 8-H), 3.06 (m, 2 H, 1-H), 3.39 (s, 3 H, OCH3), 4.05
(mc, 2 H, 3-H), 4.26 (s, 1 H, 10-H), 4.65 (s, 2 H, 5-H), 6.95 (d, J
3
= 7.5 Hz, 1 H, 6-H*), 7.06 (d, 3J = 7.5 Hz, 1 H, 7-H*) ppm. 13C
NMR (62.9 MHz, CDCl3, DEPT): δ = 22.58 (+,9-CH3), 28.46 (+,
9-CH3), 30.10 (–, C-2), 30.45 (–, C-1), 43.34 (Cquat, C-9), 45.85 (–,
C-8), 57.50 (+, OCH3), 74.76 (–, C-5), 75.45 (–, C-3), 90.43 (+, C-
10), 122.46 (+, C-6), 129.25 (+, C-7), 138.40 (Cquat), 140.73 (Cquat),
Eur. J. Org. Chem. 2010, 4687–4699
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4697

S. Schweizer, W. M. Tokan, P. J. Parsons, A. de Meijere
FULL PAPER
140.84 (Cquat), 143.72 (Cquat) ppm. MS (DCI, NH3): m/z (%) = 281
2
3
3.8 Hz, 1 H, 16-H), 0.80 (d, J = 3.8 Hz, 1 H, 16-H), 1.20 (t, J =
3
(19) [(M + NH3) + NH4+], 264 (52) [M + NH4+], 249 (92) [(M – 7.3 Hz, 3 H, OCH2CH3), 1.10–1.30 (m, 1 H), 1.25 (t, J = 7.3 Hz,
CH3) + NH4+], 232 (100) [(M – OCH3) + NH4+]. C16H22O2 (246.4): 3 H, OCH2CH3), 1.41 (m, 2 H), 1.55–1.75 (m, 7 H), 1.80–1.95 (m,
2
calcd. C 78.01, H 9.00; found C 77.79, H 9.00.
2 H), 1.85 (d, J = 14.5 Hz, 1 H, 10-H), 2.00–2.17 (m, 3 H), 2.24–
2.55 (m, 2 H), 2.85 (dd, 2J = 14.5, J = 1.2 Hz, 1 H, 10-H), 4.15 (m, 4
H, OCH2), 5.25 (m, 1 H, 3-H) ppm. 13C NMR (62.9 MHz, CDCl3,
DEPT): δ = 14.04 (+, 2 OCH2CH3), 22.74 (–, C-4*), 23.06 (–, C-
16*), 24.43 (–, CH2), 24.63 (–, CH2), 24.90 (–, CH2), 28.90 (–,
CH2), 30.25 (–, CH2), 30.58 (–, CH2), 31.52 (Cquat, C-9), 34.22 (–,
Diethyl Tetracyclo[7,4,1,01,9,02,7]tetradec-2-ene-11,11-dicarboxylate
(43): Following GP5, method A, diethyl 2-bromotetradeca-1,13-
diene-7-yne-4,4-dicarboxylate (34) (207 mg, 0.50 mmol) upon treat-
ment at 80 °C with palladium acetate (11.0 mg, 0.05 mmol), tri-
phenylphosphane (33 mg, 0.13 mmol) and silver carbonate
(414 mg, 1.50 mmol) in acetonitrile (5 mL), after 3 d, work-up and
purification by filtering over a layer each of Celite®, flash silica gel
and charcoal, afforded 124 mg (74%) of 43 as a colorless oil. Rf
C-10**), 34.32 (+, C-7), 35.33 (Cquat
,
C-1), 35.84
(–, C-8**), 56.85 (Cquat, C-11), 61.18 (–, OCH2), 61.28 (–, OCH2),
114.77 (+, C-3), 145.46 (Cquat, C-2), 171.74 (Cquat, C=O), 172.94
(Cquat, C=O) ppm. MS (70 eV, EI): m/z (%) = 362 (19) [M+ + 2
H], 361 (20) [M+ + H], 360 (100) [M+], 347 (18), 315 (10), 286 (24),
240 (24), 213 (39), 200 (30), 173 (39), 160 (47), 159 (40), 145 (74),
131 (36), 105 (23), 91 (34).
(PE/Et O, 10:1) = 0.25. IR (film): ν = 2923 (CH), 2855, 1733
˜
2
(C=O), 1448, 1251, 1202, 1173, 1087, 1077, 1041, 863 cm–1. 1H
NMR (300 MHz, C6D6): δ = 0.38 (d, 2J = 4.6 Hz, 1 H, 14-H), 0.80
2
(d, J = 4.6 Hz, 1 H, 14-H), 0.90 (m, 6 H, OCH2CH3), 1.1 (m, 1
H, 6-H*), 1.35 (m, 1 H, 5-H*), 1.63 (m, 1 H, 5-H*), 1.65–1.85 [m,
5 H, 4(6,7,8,12)-H], 1.86 (d, 2J = 14.2 Hz, 1 H, 10-H), 1.91–2.03
[m, 4 H, 4*(8,13)-H], 2.35 (m, 1 H, 12-H*), 2.85 (dd, J = 14.2, J
Acknowledgments
2
4
= 1.6 Hz, 1 H, 10-H), 3.90 (m, 4 H, OCH2), 5.28 (m, 1 H, 3-H)
This work was supported by the Land Niedersachsen and the
Fonds der Chemischen Industrie. BASF AG, Bayer AG, Degussa
AG, and Chemetall GmbH generously provided chemicals.
ppm. 13C NMR (62.9 MHz, C6D6, DEPT):
δ = 13.98 (+,
OCH2CH3), 14.19 (+,OCH2CH3), 21.33 (–, C-4), 21.46 (–, C-14),
23.12 (–, C-5*), 25.06 (–, C-13*), 26.23 (–, C-12*), 28.03 (Cquat, C-
9), 29.15 (–, C-6*), 30.51 (Cquat, C-1), 35.56 (+, C-7), 35.80 (–, C-
10), 41.22 (–, C-8), 53.90 (Cquat, C-11), 61.01 (–, 2 OCH2), 113.40
[1] a) L. F. Tietze, U. Beifuss, Angew. Chem. 1993, 105, 137–170;
Angew. Chem. Int. Ed. Engl. 1993, 32, 131–163; b) L. F. Tietze,
Chem. Rev. 1996, 96, 115–136; c) L. F. Tietze, G. Brasche,
K. M. Gericke, Domino Reactions in Organic Synthesis, Wiley-
VCH, Weinheim, 2006.
(+, C-3), 148.99 (Cquat, C-2), 170.96 (Cquat, C=O), 172.31 (Cquat
,
C=O) ppm. MS (70 eV, EI): m/z (%) = 332 (72) [M+], 258 (100)
[M+ – C4H10O], 185 (63), 173 (28), 145 (21). HRMS: calcd. for
C20H28O4 (332.4): 332.1987 (correct mass).
[2] For examples of such transition metal-catalyzed processes, see:
a) Ruthenium-catalyzed non-metathesis reactions: B. M. Trost,
F. D. Toste, A. B. Pinkerton, Chem. Rev. 2001, 101, 2067–2096;
b) Ruthenium-catalyzed metathesis reactions: T. M. Trenka,
R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18–29; S. H. Kim, N.
Bowden, R. H. Grubbs, J. Am. Chem. Soc. 1994, 116, 10801;
S. H. Kim, W. J. Zuercher, N. Bowden, R. H. Grubbs, J. Org.
Chem. 1996, 61, 1073–1081; W. J. Zuercher, M. Scholl, R. H.
Grubbs, J. Org. Chem. 1998, 63, 4291–4298; c) Nickel-catalyzed
reactions: S. Ikeda, Acc. Chem. Res. 2000, 33, 511–519; d) Co-
balt-catalyzed reactions: K. C. Nicolaou, E. J. Sorensen in:
Classics in Total Synthesis Wiley-VCH, Weinheim, 1996, pp.
153–166; F. Slowinski, C. Aubert, M. Malacria, Eur. J. Org.
Chem. 2001, 3491–3500, and references cited therein; e) Rho-
dium-catalyzed reactions: M. Fujiwara, I. Ojima, in Modern
Rhodium-Catalyzed Organic Reactions (Ed.: P. A. Evans)
Wiley-VCH, Weinheim, 2005, pp. 129–151; f) Gold- and plati-
num-catalyzed reactions, see for example: D. Hildebrandt, G.
Dyker, J. Org. Chem. 2006, 71, 6728–6733; D. J. Gorin, B. D.
Sherry, F. D. Toste, Chem. Rev. 2008, 108, 3351–3378; H.
Yeom, J. Lee, S. Shin, Angew. Chem. Int. Ed. 2008, 47, 7040–
7043; B. Crone, S. F. Kirsch, Chem. Eur. J. 2008, 14, 3514–
3522; J. Barluenga, A. Fernandez, A. Dieguez, F. Rodriguez,
F. J. Fananas, Chem. Eur. J. 2009, 15, 11660–11667; L. Liu, J.
Zhang, Angew. Chem. Int. Ed. 2009, 48, 6093–6096; E. Jime-
nez-Nunez, M. Raducan, T. Lauterbach, K. Molawi, C. R. So-
lorio, A. M. Echavarren, Angew. Chem. Int. Ed. 2009, 48, 6152–
6155; S. Kim, Y. Park, Y. Chung, Angew. Chem. Int. Ed. 2010,
49, 415–418.
Diethyl Tetracyclo[7,5,1,01,9,02,7]pentadec-2-ene-11,11-dicarboxylate
(44): Following GP5, method A, diethyl 2-bromopentadeca-1,14-
dien-8-yne-4,4-dicarboxylate (35) (214 mg, 0.50 mmol) upon treat-
ment at 70 °C with palladium acetate (11.0 mg, 0.05 mmol), tri-
phenylphosphane (33 mg, 0.13 mmol) and silver carbonate
(414 mg, 1.50 mmol) in acetonitrile (5 mL), after 3 d, work-up and
purification by filtration through a layer each of Celite®, flash silica
gel and charcoal, afforded 132 mg (76%) of 44 as a colorless oil.
R (PE/Et O, 10:1) = 0.32. IR (film): ν = 2979 , 2869, 1731 (C=O),
˜
f
2
1642 (C=O), 1382, 1130, 801, 658, 494 cm–1. H NMR (250 MHz,
1
CDCl3): δ = 0.45 (d, J = 4.7 Hz, 1 H, 15-H), 0.84 (d, 2J = 4.7 Hz,
2
1 H, 15-H), 1.21 (t, 3J = 7.1 Hz, 3 H, OCH2CH3), 1.23 (t, 3J =
7.1 Hz, 3 H, OCH2CH3), 1.20–1.55 (m, 2 H), 1.68–1.96 (m, 11 H),
2.00 (m, 2 H), 2.13 (d, 2J = 15.6 Hz, 1 H, 10-H), 2.19 (m, 2 H),
2
2.61 (d, J = 15.6 Hz, 1 H, 10-H), 4.13 (m, 4 H, OCH2), 5.26 (br.
s, 1 H, 3-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 13.91
(+, OCH2CH3), 14.00 (+, OCH2CH3), 21.45 (–, CH2), 22.72 (–,
CH2), 24.65 (–, 2 CH2), 27.62 (–, CH2), 29.14 (–, CH2), 30.77
(Cquat, C-9), 33.02 (–, CH2), 34.69 (Cquat, C-1), 35.06 (+, C-7),
37.13 (–, C-10*), 38.43 (–, C-8*), 57.08 (Cquat, C-11), 60.97 (–,
OCH2), 61.15 (–, OCH2), 113.91 (+, C-3), 146.46 (Cquat, C-2),
172.16 (Cquat, C=O), 172.75 (Cquat, C=O) ppm. MS (DCI, NH3):
m/z (%) = 710 (12) [2M + NH4+], 364 (16) [M + NH4+], 347 (100).
C21H30O4 (346.5): calcd. C 72.80, H 8.73; found C 72.84, H 8.70.
Diethyl Tetracyclo[7,6,1,01,9,02,7]hexadec-2-ene-11,11-dicarboxylate
(45): Following GP5, method A, diethyl 2-bromohexadeca-1,15-
dien-9-yne-4,4-dicarboxylate (36) (207 mg, 0.47 mmol) upon treat-
ment at 80 °C with palladium acetate (11.0 mg, 0.05 mmol), tri-
phenylphosphane (33 mg, 0.13 mmol) and silver carbonate
(414 mg, 1.50 mmol) in acetonitrile (5 mL), after 3 d, work-up and
purification by filtering over a layer each of Celite®, flash silica gel
and charcoal, afforded 51 mg (30%) of 45 as a colorless oil. Rf (PE/
[3] a) C. Hulot, S. Amiri, G. Blond, P. R. Schreiner, J. Suffert, J.
Am. Chem. Soc. 2009, 131, 13387–13398, 16587; b) C. Hulot,
G. Blond, J. Suffert, J. Am. Chem. Soc. 2008, 130, 5046–5047;
c) P. von Zezschwitz, A. de Meijere, Domino-Heck Pericyclic
Reactions in: Top. Organomet. Chem. Springer, Berlin, 2006,
pp. 49–89; d) A. de Meijere, P. von Zezschwitz, S. Bräse, Acc.
Chem. Res. 2005, 38, 413–422; e) S. Bräse, A. de Meijere, in:
Metal-Catalyzed Cross-Coupling Reactions (Eds.: A. de Mei-
jere; F. Diederich), Wiley-VCH, Weinheim, 2004, pp. 217–315;
f) J. Suffert, B. Salem, P. Klotz, J. Am. Chem. Soc. 2001, 123,
2
Et2O, 10:1) = 0.25. 1H NMR (250 MHz, CDCl3): δ = 0.22 (d, J =
4698
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4687–4699

Palladium-Catalyzed Oligocyclizations
12107–12108; g) A. de Meijere, F. E. Meyer, Angew. Chem.
1994, 106, 2473–2506; Angew. Chem. Int. Ed. Engl. 1994, 33,
2379–2411; h) Y. Zhang, E. Negishi, J. Am. Chem. Soc. 1989,
111, 3454–3456; i) Y. Zhang, G.-Z. Wu, G. Agnel, E. Negishi,
J. Am. Chem. Soc. 1990, 112, 8590–8592; j) E. Negishi, L. S.
Harring, Z. Owczarczyk, M. M. Mohamud, M. Ay, Tetrahe-
dron Lett. 1992, 33, 3253–3256.
mun. 1992, 390–392; d) H. Henniges, F. E. Meyer, U. Schick,
F. Funke, P. J. Parsons, A. de Meijere, Tetrahedron 1996, 52,
11545–11578.
W. M. Tokan, F. E. Meyer, S. Schweizer, P. J. Parsons, A.
de Meijere, Eur. J. Org. Chem. 2008, 6152–6167.
For preliminary results of a fraction of this work, see: S.
Schweizer, Z.-Z. Song, F. E. Meyer, P. J. Parsons, A. de Meijere,
Angew. Chem. 1999, 111, 1550–1552; Angew. Chem. Int. Ed.
1999, 38, 1452–1454.
P. E. Sonnet, Synth. Commun. 1976, 6, 21–26.
K. C. Brannock, J. Am. Chem. Soc. 1959, 81, 3379–3383.
[7]
[8]
[4] a) B. M. Trost, M. J. Krische, Synlett 1998, 1–16; b) B. M.
Trost, Angew. Chem. 1995, 107, 285–307; Angew. Chem. Int.
Ed. Engl. 1995, 34, 259–281; c) B. M. Trost, Y. Shi, J. Am.
Chem. Soc. 1993, 115, 12491–12509; d) B. M. Trost, Y. Shi, J.
Am. Chem. Soc. 1992, 114, 791–792; e) B. M. Trost, Acc. Chem.
Res. 1990, 23, 34–42.
[5] L. J. van Boxtel, S. Körbe, M. Noltemeyer, A. de Meijere, Eur.
J. Org. Chem. 2001, 2283–2292.
[6] a) F. E. Meyer, P. J. Parsons, A. de Meijere, J. Org. Chem. 1991,
56, 6487–6488; b) F. E. Meyer, H. Henniges, A. de Meijere, Tet-
rahedron Lett. 1992, 33, 8039–8042; c) F. E. Meyer, J. Branden-
burg, P. J. Parsons, A. de Meijere, J. Chem. Soc., Chem. Com-
[9]
[10]
[11] C. L. Starks, in: Phase Transfer Catalysis, Academic Press, New
York, 1978, pp. 128–138.
[12] J. Flahaut, P. Miginiac, Helv. Chim. Acta 1978, 61, 2275–2285.
[13] U. Jahn, P. Hartmann, I. Dix, P. G. Jones, Eur. J. Org. Chem.
2001, 3333–3355.
Received: April 26, 2010
Published Online: July 9, 2010
Eur. J. Org. Chem. 2010, 4687–4699
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4699